Author Archives: Najib Safieddine

Intraoperative Mediastinal Lymphnode Sampling vs Dissection for Subsolid Lung Nodule, Invasive Lung Cancer and Metastatetomy

Basil Nasir, Simon Turner, Gail Darling

Summary of Recommendations*

*For complete discussion, rationale, definitions and evidence, please refer to full version.

Lesion Type: Subsolid Lung Lesion

Mediastinal lymph node biopsy (sampling or dissection) may not be indicated for pure ground glass or ground glass predominant lung nodules <3cm (C:T < 0.5).

Lesion Type: Invasive Lung Cancer
  1. In patients with clinical stage I NSCLC, either a lymph node sampling, lobe-specific lymph node dissection or mediastinal lymph node dissection is recommended, with a preference given to dissection. A systemic lymph node sampling is equivalent to dissection if there is pathologic confirmation of negative mediastinal lymph nodes (either with preoperative invasive mediastinal staging or intraoperative frozen section).
  2. In patients with clinical stage II and III NSCLC undergoing surgery (including patients who undergo preoperative chemotherapy or chemoradiation), we recommend a systemic mediastinal lymph node dissection or lobe-specific systemic lymph node dissection.
  3. We recommend against the use of non-systemic or selective lymph node biopsy in patients undergoing curative-intent surgery for NSCLC.
Lesion Type: Metastatic Lesion
  1. Based on the current literature, the committee cannot recommend routine lymph node dissection or sampling in patients undergoing pulmonary metastesectomy
  2. Thoracic lymph node sampling may be reasonable in situations where the presence of lymph node disease may impact decision making.

Full Version of Recommendations

Intraoperative Mediastinal Lymph Node Biopsy in Subsolid Lung Lesions

Background

The risk of mediastinal node involvement in subsolid lung lesions is related to the extent of the solid component, as measured by the consolidation:tumour size ratio or the absolute size of the solid component. For pure ground glass or ground glass predominant (C:T<0.5) nodules less than 3cm in total size, the risk of mediastinal node involvement is low, and may approach zero. The limited utility of mediastinal node sampling or dissection in this setting should be weighed against the limited, but non-zero, morbidity and cost of the procedure. The prognostic value of mediastinal node biopsy should also be taken into account in select circumstances such as bilateral lesions where there is a question about multiple primaries vs metastatic disease. The evidence for this recommendation comes predominantly from retrospective single centre studies in Asian countries and the applicability to Canadian practice is not known at this time.  The risk of nodal involvement for ground glass lesions >3cm is less well studied but also appears low.

Recommendation

Mediastinal lymph node biopsy (sampling or dissection) may not be indicated for pure ground glass or ground glass predominant lung nodules <3cm (C:T < 0.5).

Suggested Reading

  • Moon Y, Park JK, Lee KY, Namkoong M, Ahn S. Consolidation/tumor ratio on chest computed tomography as predictor of postoperative nodal upstaging in clinical T1N0 lung cancer. World J Surg. 2018;42:2872-8.
  • Hattori A, Matsunaga, Takamochi K, Oh S, Suzuki K. Significance of lymphadenectomy in part-solid lung adenocarcinoma: Propensity score matched analysis. Ann Thorac Surg. 2018;106:989-97
  • Suzuki S, Sakurai H, Yotsukura M, et al. Clinical features of ground glass opacity-dominant lung cancer exceeding 3.0 cm in the whole tumor size. Ann Thorac Oncol. 208;105:1499-506.

References

  1. Moon Y, Shung SW, Namkoon M, Park JK. The effectiveness of mediastinal lymph node evaluation in a patient with ground glass opacity tumor. J Thorac Dis. 2016;8:2617-25.
  2. Haruki T, Aokage K, Miyoshi T, et al. Mediastinal nodal involvement in patients with clinical stage I non-small-cell lung cancer. Possibility of rational lymph node dissection. J Thorac Oncol. 2015;20:930-6.
  3. Nakamura S, Fukui T, Kawaguchi K, et al. Does ground glass opacity-dominant feature have a prognostic significance even in clinical T2aN0M0 ling adenocarcinoma? Lung Cancer. 2015;89:38-42.
  4. Hattori A, Matsunaga, Takamochi K, Oh S, Suzuki K. Importance of ground glass opacity component in clinical stage IA radiologic invasive lung cancer. Ann Thorac Surg. 2017;104:313-20. J Thorac Cardiovasc Surg. 2017;154:2102-10.
  5. Hattori A, Matsunaga, Takamochi K, Oh S, Suzuki K. Prognostic impact of a ground glass opacity in the clinical T classification of non-small cell lung cancer.
  6. Tsutani Y, Miyata Y, Nakayama H, et al. Prediction of pathologic node-negative clinical stage IA lung adenocarcinoma for optimal candidates undergoing sublobar resection. J Thorac Cardiovasc Surg. 2012;144:1365-71.
  7. Berry MR, Gao R, Kunder CA, et al. Presence of even a small ground-glass component in lung adenocarcinoma predicts better survival. Clin Lung Cancer. 2017;19:e47-51.
  8. Hayashi H, Ashizawa K, Ogihara Y, et al. Comparison between solid component size on thin-section CT and pathologic lymph node metastasis and local invasion in T1 lung adenocarcinoma. Jpn J Radiol. 2017;35:109-15.
  9. Sim HJ, Choi SH, Chae EJ, et al. Surgical management of pulmonary adenocarcinoma presenting as a pure ground-glass nodule. Eur J Cardio-Thorac Surg. 2014;46:632-6.
  10. Tsutani Y, Miyata Y, Nakayama H, et al. Appropriate sublobar resection choice for ground glass opacity-dominant clinical stage IA lung adenocarcinoma: Wedge resection or segmentectomy. Chest. 2014;145:66-71.
Intraoperative Mediastinal Lymph Node Sampling/Dissection for Primary Invasive Lung Cancer

Background

Surgical resection is established as a standard treatment for stage I non-small cell lung cancer (NSCLC). Upstaging of the tumor by the identification of lymph node disease has a significant impact on survival and therapeutic decision making1,2. The presence of hilar or mediastinal lymph node disease renders surgical resection alone less efficacious, and typically, systemic therapy is recommended. Therefore, the identification of lymph node disease is of utmost importance. Current preoperative staging techniques have reduced the number of cases with  ‘surprise N2’. Despite optimal preoperative staging with positron emission tomography (PET) and invasive mediastinal staging, a small percentage of patients with preoperative clinical node-negative status will have lymph node metastases on final pathology3.

The question of whether a mediastinal lymph node dissection provides any advantage over a systemic sampling has been debated rigorously. In this publication, we have summarized the literature and provided our interpretation and recommendations on how to handle the mediastinum during curative intent surgery for NSCLC. Studies comparing mediastinal lymph node dissection (MLND) to mediastinal lymph node sampling (MLNS) are summarized in the table4-13. We also included studies which compared MLND to lobe-specific lymph node dissection (LSD)14-18. It should be noted that many of these studies were published more than 10 years ago.

Search strategy

We conducted a Medline search of English-language studies published from 1998 to 2019. We used the Medical Subject Heading term “lymph node dissection” and then “lymph node sampling”; the terms “lung cancer,” “non-small lung cancer,” were introduced to limit the number of studies identified. Of the 106 abstracts we reviewed, 2 studies did not include a surgical population, 80 articles were excluded because they did not include a long-term comparison of MLND versus MLNS. A careful review of the remaining 24 articles was conducted, and 13 articles were excluded because of methodological issues.  The remaining 11 articles were included in this analysis. The references for each of those articles were searched, yielding an additional 2 articles that were included.

Definitions

Non-systemic or selective lymph node biopsy: In this procedure, one or multiple suspicious lymph node(s) are biopsied.

Systemic mediastinal lymph node sampling: Sampling is the removal of one or more lymph nodes guided by preoperative or intraoperative findings which are thought to be representative. Systematic sampling means a predetermined selection of the lymph node stations specified by the surgeon.

In Z0030, the definition included: For tumors in the right lung lymph node stations 2R, 4R, 7, and 10R were sampled. For tumors in the left lung, stations 5, 6, 7, and 10L were sampled. Any suspicious lymph nodes were also biopsied.

Systematic mediastinal lymph nodal dissection: All the mediastinal tissue containing the lymph nodes is dissected and removed systematically within anatomical landmarks Beside the mediastinal nodes, the hilar and the intrapulmonary lymph nodes are dissected as well

In Z0030, the definition included: For tumors on the right, all lymph tissue was removed from an area bounded by the takeoff of the right upper lobe bronchus, the innominate artery, the superior vena cava and the trachea (stations 2R and 4R). Lymph nodes in the prevascular area, adjacent to the superior vena cava, and retrotracheal nodes were removed. Complete MLND for tumors on the left involved removing all lymph tissue between the phrenic and vagus nerves extending down to the left main stem bronchus (stations 5 and 6). At the completion of the dissection, the aortopulmonary window was free of lymph tissue and the recurrent nerve was preserved. Regardless of the side of the tumor, complete subcarinal lymph node dissection was performed removing all lymph tissue caudal to the carina and both left and right mainstem bronchi (station 7). Lymph nodes in the inferior pulmonary ligament and adjacent to the caudal half of the esophagus were also removed (stations 8 and 9). When the dissection was complete, mainstem bronchi, posterior pericardium, and the esophagus were free of all lymph tissue

Lobe-specific systematic node dissection: In this procedure, the mediastinal tissue containing specific lymph node stations are excised, depending on the lobar location of the primary tumor. All ipsilateral hilar lymph node stations are dissected, but only specific mediastinal lymph node stations are resected depending on the lobar location of the primary tumor [stations 2R and 4R for right upper lobe (RUL), stations 5 and 6 left upper lobe (LUL) tumors; stations 7, 8R and 9R for right lower lobe (RLL) tumors; stations 7, 8L and 9L for left lower lobe (LLL) tumors; and stations 2R, 4R, 7, 8R and 9R for right middle lobe (RML) tumors].

Recommendations

  1. In patients with clinical stage I NSCLC, either a lymph node sampling, lobe-specific lymph node dissection or mediastinal lymph node dissection is recommended, with a preference given to dissection. A systemic lymph node sampling is equivalent to dissection if there is pathologic confirmation of negative mediastinal lymph nodes (either with preoperative invasive mediastinal staging or intraoperative frozen section).

Most studies demonstrate a higher incidence of N2 disease in MLND compared to MLNS, despite having similar demographics and tumor characteristics5,10. This would suggest that MLND may be better at detecting occult nodal disease. However, most studies that compare MLND to MLNS did not demonstrate an advantage in overall or progression-free survival. Furthermore, some studies show lower incidence of local relapse and increased cancer upstaging with MLND, and in one of these studies, there was a survival advantage to MLND5,9. Taking all these observations into consideration, one can deduce that MLND may result in better identification of occult N2 disease, perhaps better local control, but with no major impact on overall or cancer-specific survival.

The results of ACOSOG Z0030 trial have been used to justify MLNS as an alternative to MLND. This should be interpreted with caution because patients (cT1/2N0/1-less than hilar) were randomized only after a thorough mediastinal lymph node sampling and intraoperative frozen section analysis showed no evidence of lymph node disease. Therefore, the results of this study are not applicable to patients who have not had a systematic lymph node sampling which was negative, or tumors with higher T or N stage on preoperative imaging, as they were excluded from the study. Taking this into consideration, an MLNS may only be equivalent to MLND if intraoperative frozen section shows no evidence of nodal disease after systematic sampling.

All studies comparing lobe-specific lymph node dissection to MLND have shown equivalent rates of nodal detection, overall survival, and cancer-specific survival. Therefore, the committee suggests that a lobe-specific systemic dissection is equivalent to a mediastinal lymph node dissection in patients with clinical stage I NSCLC.

There are situations, however, where the incidence of nodal disease approaches zero, such as patients with semisolid nodules and small (< 2 cm), peripheral squamous cell cancers2,12.  In these patients, an MLNS may be a reasonable alternative.

  1. In patients with clinical stage II and III NSCLC undergoing surgery (including patients who undergo preoperative chemotherapy or chemoradiation), we recommend a systemic mediastinal lymph node dissection or lobe-specific systemic lymph node dissection.

Given the lack of robust data showing equivalency of MLND and MLNS in patients with known nodal disease (stage IIIA) or at high risk of having nodal disease (stage II), the committee suggests that there is insufficient evidence to show that MLNS is equivalent to MLND is these patients.

  1. We recommend against the use of non-systemic or selective lymph node biopsy in patients undergoing curative-intent surgery for NSCLC.

Reference to Other Guidelines

  • The committee fully endorses the ACCP guidlines1
  • The committee fully endorses the National Comprehensive Cancer Network (NCCN) guidelines19
  • The committee fully endorses the National Institute for Health and Care Excellence (NICE) guidelines20
  • The ESTS recommends a lymph node dissection in most cases of NSCLC undergoing curative-intent surgery2. The Scottish Intercollegiate Guidelines Network (SIGN) guidelines also suggest that lymph node sampling is inadequate21. The committee does recognize that there are situations where a dissection might be favored over a sampling. However, after reviewing the literature, we have found that the evidence was not strong enough to recommend a blanket statement. The committee disagrees with the ESTS and SIGN guidelines in recommending a dissection over sampling in all cases.

Summary of Literature

Study N Preoperative evaluation Type Rate of lymph node disease Upstaging Survival
Darling et al (Z0030) 2011 1,023 (498 MLNS, 525 MLND) CT, PET, selective invasive mediastinal staging

Only included patients who were pN0

Randomized controlled N2 4%

N1 12%

N2 4%

N1 12%

Median survival

MLNS 8.1 years

MLND 8.5 years

Wu 2002 532

(MLNS 264

MLND 268)

CT Randomized controlled N2 38% N2

MLNS 28%

MLND 48%

Median survival

MLNS 34

MLND 59

Sugi 1998 115

(56 MLNS, 59 MLND)

CT

Only included patients with tumor < 2 cm

Randomized controlled 22% MLNS

N1 5%

N2 14%

MLND

N1 7%

N2 15%

5-year survival

MLNS 84%

MLND 81%

Izbicki 1998 169

(93 MLNS, 76 MLND)

Bronchoscopy, CT, abdominal ultrasound, bone scan Randomized controlled Not stated Not stated Median disease-free interval

MLNS 24 months

MLND 48 months

(p=0.233)

Keller 2000 373

(MLNS 187

MLND 186)

CT, selective invasive mediastinal staging

Stage II and IIIa

Prospective nonrandomized 100% MLNS

N1 40%

N2 39%

Skip N2 21%

MLND

N1 41%

N2 39%

Skip N2 20%

Median survival

MLNS 29.2 months

MLND 57.5 months

Disease free survival

MLNS 21.4 months

MLND 33.2 months

(p = 0.086)

Lardinosis 2005 100 (MLNS 50 MLND 50) CT, brain CT, bone scan, CM Prospective nonrandomized 46% MLNS

N1 12%

N2 9%

MLND

N1 13%

N2 12%

Median survival

MLNS 50.9 months

MLND 51.7 months

(p = 0.4)

Massard 2006 208 (patients served as their own controls) Not stated Prospective nonrandomized N2 29%

N1 17%

“Skip N2” 12%

MLNS 15%

MLND 29%

Not stated
Su 2008 319(MLNS 180, MLND 136) CT, Brain CT, abdominal US Retrospective Not stated Not stated 5-year survival

MLNS 65.9%

MLND 76.4$

(p = 0.015)

Ma 2008 105

(MLNS 63

MLND

42)

Not stated

Included pathologic stage I patients only

Retrospective 0 N/A For tumors 2-3 cm

5 year survival

MLNS 55.8%

MLND 81.6%

For tumors < 2cm

No difference

Takizawa 2008 119

(61 MLNS, 58 MLND)

CT, selective invasive mediastinal staging Retrospective 12.6% N2 = 13.8% in MLND

N2 = 11.5% in MLNS

5-year cancer specific survival

MLNS 76.2%

MLND 78%

Lobe-specific dissection (LSD) versus mediastinal lymph node dissection (MLND)
Okada 2006 LSD 377

MLND 358

Not stated

Included only clinical stage I

Retrospective 6.1 LSD

N1 5.6%

N2 0.5 %

MLND

N1 5.3%

N2 0.8%

5-year disease free survival

LNS 76.4%

MLND 73.4% (p = NS)

5-year survival

LNS 83.2 %

MLND 79.7%

(P = NS)

Ishiguro 2010 LSD 137

MLND 625

Not states

Included stage cIA – cIIIB

Retrospective Not stated N/A 5 year survival

LSD 76%

MLND 71.9%

(p = NS)

Maniwa 2013 335

LSD 129

MLND 206

CT, PET, Brain MRI

Included stage I-II

Retrospective N1 7%

N2 6%

LSD

N1 8.2%

N2 4.2 %

MLND

N1 8.3%

N2 7.7%

5 year survival

LNS 89.7%

MLND 86.6%

(p = NS)

5 year disease free survival

LNS 76.4%

MLND 77.7%

(p = NS)

Hishida 2016 5392

LSD 1268

MLND 4124

CT, selective PET and invasive mediastinal staging

Included stage cI-cII

Retrospective Not stated N2

LSD 8.4%

MLND 12.7%

pN2 disease outside the LSD area and accessible only by SND = 3.2%

5-year survival

LSD 81.5%

MLND 75.9%

(p =

Adachi 2017 488

MLNS 153

LSD 145

MLND 190

CT, PET

Included cT1a–2b N0–1 M0

Retrospective N1 9%

N2 9%

N1

MLNS 7.2%

LSD 7.6%

MLND 11.1%

N2

MLNS 3,3%

LSD 9%

MLND 13.1%

5-year survival

MLNS 70.9%

LSD 74.7%

MLND 73.8%

(p = NS)

References

  1. Howington JA, Blum MG, Chang AC, Balekian AA, Murthy SC. Treatment of Stage I and II Non-small Cell Lung Cancer; Diagnosis and Management of Lung Cancer,3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2013; 143(5)(Suppl):e278S–e313S
  2. Lardinois D, De Leyn P, Van Schil P, Porta RR, Waller D, Passlick B, Zielinski M, Lerut T, Weder W. ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer. Eur J Cardiothorac Surg. 2006 Nov;30(5):787-92
  3. Nasir BS, Yasufuku K, Liberman M. When Should Negative Endobronchial Ultrasonography Findings be Confirmed by a More Invasive Procedure? Ann Surg Oncol. 2018 Jan;25(1):68-75
  4. Darling GE , Allen MS , Decker PA , et al . Number of lymph nodes harvested from a mediastinal lymphadenectomy: results of the randomized, prospective American College of Surgeons Oncology Group Z0030 trial. Chest. 2011;139(5):1124-1129.
  5. Wu Yl, Huang ZF, Wang SY, Yang XN, Ou W. A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer. 2002 Apr;36(1):1-6.
  6. Sugi K, Nawata K, Fujita N, Ueda K, Tanaka T, Matsuoka T, Kaneda Y, Esato K. Systematic lymph node dissection for clinically diagnosed peripheral non-small-cell lung cancer less than 2 cm in diameter. World J Surg. 1998 Mar; 22(3):290-
  7. Izbicki JR, Passlick B, Pantel K, Pichlmeier U, Hosch SB, Karg O, Thetter O. Effectiveness of radical systematic mediastinal lymphadenectomy in patients with resectable non-small cell lung cancer: results of a prospective randomized trial. Ann Surg. 1998 Jan; 227(1):138-44
  8. Keller SM, Adak S, Wagner H, Johnson DH. Mediastinal lymph node dissection improves survival in patients with stages II and IIIa non-small cell lung cancer. Eastern Cooperative Oncology Group. Ann Thorac Surg. 2000 Aug;70(2):358-65
  9. Lardinois D, Suter H, Hakki H, Rousson V, Betticher D, Ris HB. Morbidity, survival, and site of recurrence after mediastinal lymph-node dissection versus systematic sampling after complete resection for non-small cell lung cancer. Ann Thorac Surg. 2005 Jul; 80(1):268-74
  10. Massard G, Ducrocq X, Kochetkova EA, Porhanov VA, Riquet M. Sampling or node dissection for intraoperative staging of lung cancer: a multicentric cross-sectional study. Eur J Cardiothorac Surg. 2006 Jul;30(1):164-7
  11. Su X , Wang X, Long H, Fu J, Lin P, Zhang Let al. . Mediastinal lymph node dissection affects survival in patients with stage I non-small cell lung cancer. Thorac Cardiovasc Surg 2008;56:226–30.
  12. Ma K, Chang D, He B, Gong M, Tian F, Hu X, Ji Z, Wang T. Radical systematic mediastinal lymphadenectomy versus mediastinal lymph node sampling in patients with clinical stage IA and pathological stage T1 non-small cell lung cancer. J Cancer Res Clin Oncol. 2008 Dec; 134(12):1289-9
  13. Takizawa H, Kondo K, Matsuoka H, Uyama K, Toba H, Kenzaki K, Sakiyama S, Tangoku A, Miura K, Yoshizawa K, Morita J. Effect of mediastinal lymph nodes sampling in patients with clinical stage I non-small cell lung cancer. J Med Invest. 2008 Feb;55(1-2):37-43.
  14. Okada M, Sakamoto T, Yuki T, et al. Selective mediastinal lymphadenectomy for clinico-surgical stage I non-small cell lung cancer. Ann Thorac Surg 2006;81:1028-32
  15. Ishiguro F, Matsuo K, Fukui T, et al. Effect of selective lymph node dissection based on patterns of lobe-specific lymph node metastases on patient outcome in patients with resectable non-small cell lung cancer: a large-scale retrospective cohort study applying a propensity score. J Thorac Cardiovasc Surg
  16. Maniwa T, Okumura T, Isaka M, et al. Recurrence of mediastinal node cancer after lobe-specific systematic nodal dissection for non-small-cell lung cancer. Eur J Cardiothorac Surg 2013;44:e59-64.
  17. Hishida T, Miyaoka E, Yokoi K, et al. Lobe-Specific Nodal Dissection for Clinical Stage I and II NSCLC: Japanese Multi-Institutional Retrospective Study Using a Propensity Score Analysis. J Thorac Oncol 2016;11:1529-37
  18. Adachi H, Sakamaki K, Nishii T, et al. Lobe-specific lymph node dissection as a standard procedure in surgery for non-small-cell lung cancer: A propensity score matching study. J Thorac Oncol 2017;12:85-93
  19. National Comprehensive Cancer Network (NCCN) guidelines. Lung Cancer. www.nccn.org
  20. Maconachie R, Mercer T, Navani N, McVeigh G. Lung Cancer: Diagnosis and Management: summary of updated NICE guidelines. BMJ 2019; 28:364-1049
  21. Scottish Intercollegiate Guidelines Network (SIGN). Management of Lung Cancer. Edinburgh: SIGN 2014. SIGN publication No. 137. Available from URL http://www.sign.ac.uk
Intraoperative Mediastinal Lymph Node Sampling/Dissection - Metastatectomy

Background

Pulmonary metastesectomy in selected patients is associated with improved survival1. The role for lymph node sampling or dissection during curative intent surgery for lung cancer has been established2. However, the role of lymph node evaluation during pulmonary metastesectomy for extrathoracic malignancy is not well defined. Many questions remain unanswered, such as the need for routine versus selective mediastinal lymph node evaluation and whether a lymph node dissection is needed or is sampling enough. Most importantly, and perhaps even more difficult to answer, is there a therapeutic benefit to mediastinal lymph nodes that contain metastases from extrathoracic malignancy?

We have made a few observations form examining the literature. First, the icnidecne o f lymph node metastases are highest in series that perform an extensive lymph node dissection3. The most commonly examined histology is colorectal primary tumors, which have an incidence of thoracic lymph node metastases of 7-16%4-9.

Second, that presence of thoracic lymph node metastases significantly impacts survival negatively. In ost series, the overall survival drops by approximately 50%3-9. Additionally, 5 year survival approaches zero in some series6,8.

Third, there is no conclusive evidence that resecting lymph nodes with metastatic deposits improves survival. There is no comparison or randomized trial that shows improvement if a lymph node dissection will result in better control, and based on the one series, the majority of patients will progress in distant sites8.

Recommendations

  1. Based on the current literature, the committee cannot recommend routine lymph node dissection or sampling in patients undergoing pulmonary metastesectomy
  2. Thoracic lymph node sampling may be reasonable in situations where the presence of lymph node disease may impact decision making.

There may be situations where the presence of lymph node metastases may impact decision making. For example, the decision to give additional systemic therapy or the decision to proceed with contralateral metastesectomy in the setting bilateral pulmonary metastases. It may be reasonable in theses situations to abort a contralateral metastesectomy if thoracic lymph node metastases are identified. Therefore, a mediastinal dissection or sampling may be beneficial to help with the decision making.

Summary of Literature

Study N Type Cancer types Rate of lymph node disease Results
Loehe 2001 63 – MLND Retrospective Colon / rectum = 18

Renal = 16

Nasopharyngeal = 8

Sarcoma = 8

Gynecologic = 6

Miscellaneous = 7

14.3% There was no significant difference in the cumulative survival depending on the mediastinal lymph node status
Saito 2002 165

135 – MLND

30 – No MLND

Retrospective Colon / rectum = 165 12% 5-year survival was 48.5% for the patients without hilar

or mediastinal lymph node metastasis, versus 6.2% at 4

years for the patients with metastases

Ercan 2004 833

70 – MLND

763 – No LNS

Retrospective Colon = 44

Renal cell = 13

Melanoma = 6

Endometrial = 2

Salivary = 2

Urothelial = 3

28.6% 3-year survival for patients

with negative lymph nodes was 69% as compared with

only 38% for those with positive lymph nodes

Pfannschmidt 2006 254 – MLND Retrospective Colon /rectum = 114

Renal = 62

Soft tissue sarcoma = 48

Osteosarcoma = 21

32.7% Median survival

N0 – 63.9 months

N1 – 32.7 months

N1 + N2 = 20.7 months

Welter 2007 169 Retrospective Colon / rectum = 169 16.7% Median survival (months)

N0 = 48.7

Intrapulmonary LNM = 86

Hilar LNM = 24.5

Mediastinal LNM = 34.7

5 year survival

N0 = 42.5%

Intrapulmonary LNM = 78.5%

Hilar LNM = 0%

Mediastinal LNM = 0%

Hamaji 2012 518

319 – MLND

199 – No MLND

Retrospective Colon / rectum – 518 7% Median survivals

no LND = 52 months

negative LND = 58.5 months

positive LND = 34 months

Kudelin 2013 116 – MLND Retrospective Renal = 116 46.6% Median survival

N0 – 71.9 months

N+ – 37.1 months

References

  1. Pastorino U, Buyse M, Friedel G, et al. Long-term results of lung metastasectomy: prognostic analysis based on 5206 cases. J Thorac Cardiovasc Surg 1997;113:37–49.
  2. Howington JA, Blum MG, Chang AC, Balekian AA, Murthy SC. Treatment of Stage I and II Non-small Cell Lung Cancer; Diagnosis and Management of Lung Cancer,3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2013; 143(5)(Suppl):e278S–e313S
  3. Kudelin N, Bölükbas S, Eberlein M, Schirren J. Metastasectomy with standardized lymph node dissection for metastatic renal cell carcinoma: an 11-year single-center experience. Ann Thorac Surg. 2013 Jul;96(1):265-70
  4. Loehe F, Kobinger S, Hatz RA, Helmberger T, Loehrs U, Fuerst H. Value of systematic mediastinal lymph node dissection during pulmonary metastasectomy. Ann Thorac Surg. 2001 Jul;72(1):225-9
  5. Saito Y, Omiya H, Kohno K, Kobayashi T, Itoi K, Teramachi M, Sasaki M, Suzuki H, Takao H, Nakade M. Pulmonary metastasectomy for 165 patients with colorectal carcinoma: A prognostic assessment. J Thorac Cardiovasc Surg. 2002 Nov;124(5):1007-13.
  6. Ercan S, Nichols FC 3rd, Trastek VF, Deschamps C, Allen MS, Miller DL, Schleck CD, Pairolero PC. Prognostic Significance of Lymph Node Metastasis Found During Pulmonary Metastasectomy for Extrapulmonary Carcinoma. Ann Thorac Surg 2004;77:1786 –91.
  7. Pfannschmidt J, Klode J, Muley T, Dienemann H, Hoffmann H. Nodal Involvement at the Time of Pulmonary Metastasectomy: Experiences in 245 Patients. Ann Thorac Surg 2006;81:448 –54
  8. Welter S, Jacobs J, Krbek T, Poettgen C, Stamatis G. Prognostic impact of lymph node involvement in pulmonary metastases from colorectal cancer. Eur J Cardiothorac Surg. 2007 Feb;31(2):167-72
  9. Hamaji M1, Cassivi SD, Shen KR, Allen MS, Nichols FC, Deschamps C, Wigle DA. Is lymph node dissection required in pulmonary metastasectomy for colorectal adenocarcinoma? Ann Thorac Surg. 2012 Dec;94(6):1796-800

CATS Position on E-cigarettes

Background

The major reason people will use e-cigarettes, or vape as it is commonly known, is for nicotine intake. The e-cigarette devices and the available products for vaporization have been sold by companies as an alternative to combustible tobacco cigarettes and their known harmful effects. Other substances for recreational use, marijuana and illicit drugs, along with flavoured non-nicotine vapours are also known uses of the devices. The health effects of these substances is even less well studied compared to nicotine vaporization

The positions and recommendations herein should be regarded as the product of a non-systematic literature review. They are however in accordance (with some specific societal variations) with the positions advocated by the American Lung Association and the World Health Organization. Our hope is that this recommendation is of utility to CATS members and other stakeholders including our patient community.

Recommendations

  • At present the e-cigarettes and nicotine substances for vaporization can cause lung and heart disease with a still unknown concern for carcinogenesis. The recently reported deaths and serious respiratory illnesses worldwide associated with e-cigarettes raises serious concerns regarding their safety. We strongly recommend against their use until adequate regulation is in place.
  • Lung health advocacy groups are concerned with respect to the safety of these products as a means for nicotine intake. More extensive and long-term studies to any potentially harmful effects are needed.
  • Their use by young people has been shown to increase the use of combustible tobacco products and therefore is a concern and is strongly discouraged.

Evidence

The review of evidence to date suggests the following with respect to e-cigarettes:

  1. No randomized trials of traditional cigarettes versus e-cigarettes to compare health or disease outcomes.
  2. No long-term observational trials examining health risks of e-cigarettes presently.
  3. A number of societies have published position papers on their concerns for patient health related to e-cigarettes as they are a tobacco related product.
  4. Most studies of e-cigarettes are related to the analysis of the vapour and identification of lung and cardio-toxic by-products along with identification of known carcinogens.
    • Key findings:
      • Cytotoxic agents propylene glycol and vegetable glycerin are the main ingredients of e-cigarettes.
      • Acetaldehyde, acrolein and formaldehyde are present in e-cigarette vapours and are both lung and cardio-toxins.
      • Second hand vapours include nicotine, diacetyl, benzene, nickel, tin and lead.
      • Vapours from e-cigarettes have been shown to contain known carcinogens such as: tobacco specific nitrosamines, nickel and toluene.
  5. Though a safer alternative to combustible tobacco products use of e-cigarettes increases the use by youth and young adults of combustible tobacco products.

Recommendations from a Review and Analysis of Strategies for Prediction, Prevention and Management of Post-operative Atrial Fibrillation after Non-cardiac Thoracic Surgery.


Background:

Atrial fibrillation (AF) is the most commonly sustained arrhythmia after non-cardiac thoracic surgery, occurring between 12%-44% of pulmonary and esophageal resections, and is associated with a significant increase in post-operative morbidity, length of stay (LOS), intensive care unit (ICU) admission and mortality ([i],[ii]). Patients who develop postoperative atrial fibrillation (POAF) often experience an increased LOS of 2 to 14 days ([iii]). If sustained, it can increase the patient’s risk of thromboembolic events ([iv]). As an independent risk factor of stroke in the 30 days following development of new sustained AF ([v]), anticoagulation is critical ([vi]). AF is associated with increased mortality risk after esophagectomy (mortality increase from 4.8 to 8.1%, p=0.04) ([vii]) and decreased long-term survival after lobectomy (HR 3.75; 95% CI 1.44 to 9.08) (1). AF is both common and impactful, efforts to effectively and optimally predict, prevent and manage POAF is critical to improving quality of thoracic surgical care.

Our review and analysis aimed to provide a practical, feasible and clinically applicable strategy for the prediction, prevention and management of POAF in patients undergoing non-cardiac thoracic surgery. Below are the recommendations developed from our review and analysis, as well as an algorithm to guide individualized evidence-based management of POAF.

Recommendation

  1. Multiple existing predictive models are capable of identifying patients at increased risk for POAF; however clinical application of these risk models first requires external validation, followed by ongoing evaluation and improvement over time.
  2. Prophylactic therapy with beta-blocker agents, amiodarone, calcium-channel blockers (CCB) and magnesium may be considered to reduce the risk of POAF; however, providing prophylaxis to all patients is not recommended because the exposure of all patients to the risk of adverse events outweighs the benefit experienced by only a few patients in preventing POAF. The approach of implementing prophylaxis only in high-risk patients only to reduce incidence and severity of POAF is promising yet unproven, and requires further study to evaluate safety and effectiveness.
  3. For patients with new onset POAF who develop acute hemodynamic instability, immediate synchronized electrocardioversion is recommended and consideration of echocardiogram.
  4. Hemodynamically stable patients with POAF should receive incremental dosing of rate control therapy with continuous cardiac monitoring until a heart rate of <110 BPM is achieved. If the patient has known decompensated heart failure or ejection fraction <35%, consider the least negatively inotropic agent, namely amiodarone. If no decompensated heart failure, initial trial of low trial dose of beta-blocker (e.g. 2 mg metoprolol IV push) should be given followed by repeat dosing if beneficial effect witnessed (e.g. lowering HR) and no adverse events (e.g. hypotension, bronchospasm, bradycardia) until desired effect; or if no effect observed on heart rate or blood pressure, consider CCB (e.g. 5 mg diltiazem IV push), with repeat dosing if beneficial effect and no adverse events to achieve rate control.
  5. To augment effect of either beta-blocker or CCB, consider digoxin to further augment effectiveness of rate control and minimize adverse events.
  6. Early assessment and correction of underlying POAF triggers may help facilitate early return to sinus rhythm (such as pneumothorax, pneumonia, pulmonary embolism, infection, bleeding or electrolyte abnormalities).
  7. Cardioversion should be reserved for patients who cannot tolerate rate control agents or who, after 48h, continue to have POAF despite rate control.
  8. The choice of antiarrhythmic agent should be selected in accordance with the patient’s comorbidities and the agents side effect profile.
  9. Further formal evaluations of standardized protocols to predict, prevent and manage POAF are warranted to evaluate impact on incidence, duration and severity of POAF.
  10. Antithrombotic therapy to reduce the risk of stroke in patients with persistent AF should be considered if POAF persists >48h, and should be individualized based on patient’s risk factors for thromboembolic event (congestive heart failure, hypertension, diabetes, previous thromboembolic event, peripheral vascular disease) and post-operative bleeding risk.

Abbreviations: POAF, post-operative atrial fibrillation; CCB, calcium channel blocker; BPM, beats per minute.

Abbreviations: IV, intravenous; O2, oxygen; ECG, electrocardiogram; CBC, complete blood count; LOC, level of consciousness; HR, heart rate; HF, heart failure; EF, ejection fraction, CHF, congestive heart failure; HTN, hypertension; DM, diabetes mellitus; TIA, transient ischemic attack, CXR, chest x-ray; TEE, trans-esophageal echocardiogram; LMWH, low molecular weight heparin; ASA, acetylsalicylic acid.

References

[i] Imperatori, A., Mariscalco, G., Riganti, G., et al. (2012b). Atrial fibrillation after pulmonary lobectomy for lung cancer affects long-term survival in a prospective single-center study. Journal of Cardiothoracic Surgery, 7, 4. https://doi.org/10.1186 /1749-8090-7-4

[ii] Amar D, Zhang H, Shi W, et al. Brain natriuretic peptide and risk of atrial fibrillation after thoracic surgery. The Journal of Thoracic and Cardiovascular Surgery. 2012 Nov 1;144(5):1249–53.

[iii] Polanczyk, C.A., Goldman, L., Marcantonio, E.R., et al. Supraventricular arrhythmia in patients having non cardiac surgery: clinical correlates and effect on length of stay. The Annals of Internal Medicine. 1998; 129: 279–285

[iv] Investigators, T. A. F. F. I. of R. M. (AFFIRM). (2002). A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation. New England Journal of Medicine, 347(23), 1825–1833. https://doi.org/10.1056/NEJMoa021328

[v]  Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. The Lancet. 2008 May 31;371(9627):1839–47.

[vi]  Camm, A.J., Lip G.Y.H, De Caterina R., et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation An update of the 2010 ESC Guidelines for the management of atrial fibrillation Developed with the special contribution of the European Heart Rhythm Association. Europace. 2012 Oct 1;14(10):1385–413.

[vii] Rao, V. P., Addae-Boateng, E., Barua, A., et al. (2012). Age and neo-adjuvant chemotherapy increase the risk of atrial fibrillation following oesophagectomy. European Journal of Cardio-Thoracic Surgery, 42(3), 438–443. https://doi.org/10.1093/ejcts /ezs085


Authors:
H Smith, MD ; C, Yeung, MD2; S Gowing, MD2; MM Sadek, MD, FRCPC3; DE Maziak, MD, FRCSC2; S Gilbert, MD, FRCSC2; FM Shamji MD, FRCSC2; PJ Villeneuve, MD, FRCSC2; RS Sundaresan MD FRCSC2, AJE Seely MD, PhD, FRCSC
[1] Division of General Surgery, The Ottawa Hospital, University of Ottawa
[2] Division of Thoracic Surgery, The Ottawa Hospital, University of Ottawa
[3] Division of Cardiology, The Ottawa Hospital, University of Ottawa

Correspondence to:
Heather Smith
Department of Surgery, Division of General Surgery, The Ottawa Hospital
501 Smyth Rd, Ottawa, ON K1H 8L6
Email: hesmith@toh.ca
Telephone: (613) 789-5555

Author’s Contribution:
(II) Administrative support: HS
(III) Provision of study materials or patients: NA
(IV) Collection and assembly of data: HS, AS, MS, FS, DM, SS, AS
(V) Data analysis and interpretation: HS, AS, MS, FS, DM, SS, AS
(VI) Manuscript writing: All authors
(VII) Final approval of manuscript: All authors


Recommendation Regarding Brain Imaging in Lung Cancer Staging.


Background:

Brain imaging is an important component of the accurate staging of newly diagnosed patients with non-small cell and small cell lung cancer. However, there is a paucity of robust evidence in the literature to give guidance as to the best imaging modality and those that should have brain imaging performed. Most recommendations come from large professional bodies such as NCCN, ESMO, NICE and the ACCP. Brain MRI is generally felt to be the most accurate modality. CT is an acceptable alternative if access to MRI is not possible or if there would be considerable delay in patient workup if waiting for an MRI to be completed.

Recommendation

Based on a review of the most recent guidelines from the organizations noted above:

  • Brain imaging is absolutely recommended for:
    • Patients with Clinical Stage III and IV NSCLC
    • Patients with symptoms (H/A, slurred speech etc…)
    • Patients with Small Cell Lung Cancer
  • Brain imaging for clinical Stage II NSCLC continues to be a matter of debate, however some national bodies have recommended it particularly NCCN.
  • MRI is the modality of choice over CT but depends on availability, wait time and cost.

Suggested Reading List

  • National Comprehensive Cancer Network (NCCN) – Clinical Practice Guidelines in Oncology, Non-Small Cell Lung Cancer v6.2018. http://www.nccn.org/default.aspx
  • National Institute for Health and Care Excellence (NICE) – Lung cancer: diagnosis and management (2011) NICE guideline CG121. https://pathways.nice.org.uk/pathways/ lung-cancer
  • Silvestri G. et. al., Methods for Staging Non-small Cell Lung Cancer.
  • Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2013; 143(5) (Suppl):e211S–e250S.
  • ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Early and locally advanced non-small-cell lung cancer (NSCLC). Ann Oncol (2017) 28 (suppl 4): iv1–iv21
  • Vernon J, Andruszkiewicz N, Schneider L, Schieman C, Finley CJ, Shargall Y, Fahim C, Farrokhyar F, Hanna WC. Comprehensive clinical staging for resectable lung cancer: Clinico-pathological correlations and the role of brain imaging. J Thorac Oncol. 2016 Nov;11(11):1970-1975

Surgical Wait-Times for Resectable Lung Cancer.


Background:

Timely care is a fundamental component of quality. Although what constitutes timely care in lung cancer remains a subject of debate, many international/national/regional bodies have set consensus targets for wait times. Given the lack of level I evidence, the committee reviewed various recommendations and adopted one best supported by the available evidence for a Canadian context.

CATS recognizes all too well that thoracic surgeons are only able to achieve timely care if adequate resources (e.g. OR time, CT guided biopsies, imaging resources including PET scans to mention a few) are made available in a timely fashion. CATS also recognizes that local/provincial factors and limitations vary. CATS hopes that adopting such recommendations based on best available evidence helps empower surgeons and care providers to demand the resources they need to deliver quality care.

Recommendation

  • For patients with lung cancer whose primary treatment modality is surgical resection, time from referral* for initial consultation to resection should not exceed 6 weeks**.

* We purposefully avoided specifying time from referral to consultation as centres may have different preferences about performing certain investigations prior to consultation or starting with a consultation

** We believe that in the majority of cases, surgeons do have an understanding early on as to which patients will likely be operable and so diagnostic, staging and physiologic investigations can be arranged in parallel making 6 weeks a realistic goal.

Summary of Literature

Several guidelines highlighting recommended wait times based on different time intervals in the treatment pathway have been published. The table below highlights some of these guidelines.  Two main areas of debate in the wait-times literature persist: 1) the effect of timely care on survival and 2) the ability of healthcare providers to meet established (recommended) wait time guidelines.

No strong association between earlier initiation of anticancer treatment and improved survival has been reported. In addition, recent publication out of McGill University, demonstrated that roughly 60% of patients met the target of first contact, and only 62% of cases were operated on within the recommended time frame (28 days) after being initially seen by a surgeon. Interventions that are associated with improved timeliness include: nurse-led care coordination, access to multidisplinary meetings and a standardized diagnostic process.

References

Olson JK, Shultz EM, Gould MK. Timeless of care in patient with lung caner: a systematic review. Thorax 2009. Sep; 64(9): 749-56.

Kasymjanova G, Small D. Cohen V.  et al. Lung Cancer care trajectory at a Canadian center: an evaluation of how wait times affect clinical outcomes. Curr Oncol. 2017 October 24(5): 302-309

Time Interval Recommended wait time (days)
  British Thoracic Society UK National Health Service RAND Corporation American College of Chest Physician Cancer Care Ontario
Referral → Lung cancer specialist 7 14
Lung cancer speciality → Diagnosis 30 35
Referral → 1st Treatment 62 62 60
Lung specialist → Surgery 56 104 68
Diagnosis → Surgery Consult 60
Surgery Consult → Surgery 28 14-84
Surgery → Adjuvant Chemotherapy 120 120
Diagnosis → 1st Treatment 30 31 42 35 52
Diagnosis → Chemotherapy 28 30 42 39
Diagnosis → Radiotherapy 42
Decision to treat → Non-surgical treatment 7-28
Ready to treat → Radiation 28

Adapted from: Curr Oncol. 2017 October 24(5): 302-309

 


Recommendation for Thoracic Surgery Perioperative VTE Prophylaxis.


Background:

It is now widely accepted that the true incidence of post-op VTE following lung and esophageal resection is largely under-reported. A large range of incidence has been reported, with variations mainly related to different detection methods, type and duration of prophylaxis, and the subclinical nature of a significant proportion of VTE occurrence. Thoracic surgery poses an increased risk of postop VTE given the high prevalence of oncologic surgery, the protracted post-operative recovery, and the direct manipulation of the lung and pulmonary vascular anatomy.

CATS Recommendations

CATS members continue to be involved in research evaluating the optimal method and duration for post-thoracic surgery VTE prophylaxis. The committee recognizes however the paucity of high-level evidence in this field. As higher level evidence emerges, CATS hopes that a unified approach to postop VTE prophylaxis can serve as a starting point to adopt new guidelines for in-hospital and post discharge care.

  1. Post Thoracic surgery in-hospital prophylaxis = LMWH or LDUH +/- mechanical compression
  2. No recommendation for extended prophylaxis = use at surgeon’s discretion
  3. Symptomatic postop VTE = Thrombosis referral + therapeutic anticoagulation

Summary of the Evidence

  • Most data is based on retrospective single-institution cohort studies.
    • Results are challenged by the retrospective nature of the studies, dependence on symptomatic diagnosis and not asymptomatic screening, and lack of recognition of de novo PE without DVT
    • Estimates of postop incidence: 5-15.2%
  • More recent research has evaluated prevalence of post-lung resection VTE using screening strategies in a prospective fashion
    • Prospective screening studies
      • CTPA 7-15 days postop = prevalence of 14%
      • B/L Doppler U/S + CTPA @ 30-days postop = prevalence 12.1%
    • 23% of VTE occur post-discharge & Post-pneumonectomy peak incidence à >7 days postop
    • Cohort of 2,373 cancer patients identified that 40% of VTE occurred >21 days post discharge
  • Canadian Delphi Survey including CATS members (Journal Thorac Dis. 2017 Jan; 9(1)80-87)
    • Strong agreement in identifying risk factors for VTE, and which of those factors may potentially influence the decision for extended post-hospital discharge prophylaxis.
    • Limited agreement on the type of prophylaxis (pharmacological, mechanical and/or both), as well as the initiation and duration of thromboprophylaxis—indicating high degree of variability
    • The only reliable factor of agreement was the use of LMWH in hospital

ACCP 9th Edition Guidelines for Thoracic Surgery

  • Moderate risk for VTE + not high bleeding risk à LDUH or LMWH (Grade 2B), or MCS (Grade 2c)
  • High risk for VTE + not high bleeding risk à LDUH or LMWH (Grade 1B) + MCS (Grade 2C)
  • High risk for Major bleeding à MCS with optimally applied IPC (Grade 2C)
  • No recommendation for extended post-discharge prophylaxis.

Follow-up and Surveillance Recommendations for Patients Treated Curatively for Lung Cancer.


Background:

Despite advances in the care of patients with NSCLC, the overall 5-year survival for patients treated with curative intent remains poor. The rationale for surveillance following the treatment of lung cancer is the detection of recurrent disease or a new primary lung cancer, no randomized data exist to support specific recommendations for surveillance modality and interval. Most recommendations are based on expert consensus and cohort studies, and the effect of surveillance on survival continues to be debated. Data extrapolated from screening trials does demonstrate a survival benefit to the detection of early stage cancers and most guideline-setting groups recommend a surveillance strategy involving regular clinical examinations and imaging. 1-8, 10-16

Recommendations

  • Surveillance for early recurrence or new primaries in patients treated with curative intent for NSCLC:
    • Low dose CT chest +/- contrast q6mo in years 1 and 2 1-5,9,17,18
    • Low dose CT chest +/- contrast q12mo years thereafter1-5,9,17,18
  • CT dose (i.e. Low dose vs Minimal dose) and the use of contrast is controversial. There are no data to suggest one dose over another. Extrapolation of data from the National Lung Cancer Screening Trial would suggest Low dose CT provides good sensitivity for the detection of early stage cancers.4,5,6
  • Surveillance for early recurrence or new primaries in patients treated with curative intent for SCLC:
  • Surveillance recommendations for surveillance post curative intent treatment of SCLC are based on expert consensus and parallel those for NSCLC.
  • Contrast enhanced CT chest may provide superior assessment of mediastinal nodal involvement18

References

  1. Calman L, Beaver K, Hind D, Lorigan P, Roberts C, Lloyd-Jones M. Survival benefits from follow-up of patients with lung cancer: a systematic review and meta-analysis. J Thorac Oncol. 2011;6(12):1993-2004.
  2. Sugimura H, Yang P. Long-term survivorship in lung cancer: a review. Chest.2006;129(4):1088-97
  3. Srikantharajah D, Ghuman A, Nagendran M, Maruthappu M. Is computed tomography follow-up of patients after lobectomy for non-small cell lung cancer of benefit in terms of survival? Interact Cardiovasc Thorac Surg. 2012;15(5):893-8.
  4. Hanna WC, Paul NS, Darling GE, Moshonov H, Allison F, Waddell TK, et al. Minimal-dose computed tomography is superior to chest x-ray for the follow-up and treatment of patients with resected lung cancer. J Thorac Cardiovasc Surg. 2014;147(1):30-5.
  5. National Lung Screening Trial Research Team, Church TR, Black WC, Aberle DR, Berg CD, Clingan KL, et al. Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med. 2013;368(21):1980-91.
  6. Crabtree TD, Puri V, Chen SB, et al. Does the method of radiologic surveillance affect survival after resection of stage I non-small cell lung cancer? J Thorac Cardiovasc Surg 2015;149:45-52, 53 e41-43.
  7. Aberle DR, DeMello S, Berg CD, Black WC, Brewer B, Church TR, et al. Results of the two incidence screenings in the National Lung Screening Trial. N Engl J Med. 2013;369(10):920-31.
  8. Erb CT, Su KW, Soulos PR, et al. Surveillance practice patterns after curative intent therapy for stage I non-small-cell lung cancer in the medicare population. Lung Cancer 2016;99:200-207. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27565940.
  9. Colt HG, Murgu SD, Korst RJ, et al. Follow-up and surveillance of the patient with lung cancer after curative-intent therapy: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e437S-454S. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23649451.
  10. Lou F, Huang J, Sima CS, et al. Patterns of recurrence and second primary lung cancer in early-stage lung cancer survivors followed with routine computed tomography surveillance. J Thorac Cardiovasc Surg 2013;145:75-81; discussion 81-72. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23127371.
  11. Srikantharajah D, Ghuman A, Nagendran M, Maruthappu M. Is computed tomography follow-up of patients after lobectomy for non-small cell lung cancer of benefit in terms of survival? Interact Cardiovasc Thorac Surg 2012;15:893-898. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22859511.
  12. Dane B, Grechushkin V, Plank A, et al. PET/CT vs. non-contrast CT alone for surveillance 1-year post lobectomy for stage I non-small-cell lung cancer. Am J Nucl Med Mol Imaging
  13. Nakamura R, Kurishima K, Kobayashi N, et al. Postoperative follow-up for patients with non-small cell lung cancer. Onkologie. 2010;33(1-2):14-18
  14. Johnson BE. Second lung cancers in patients after treatment for an initial lung cancer. J Natl Cancer Inst 1998; 90: 1335–1345.
  15. Demicheli R, Fornili M, Ambrogi F et al. Recurrence dynamics for non-small-cell lung cancer: effect of surgery on the development of metastases. J Thorac Oncol 2012; 7: 723–730.
  16. Toba H, Sakiyama S, Otsuka H et al. 18F-fluorodeoxyglucose positron emission tomography/computed tomography is useful in postoperative follow-up of asymptomatic non-small cell lung cancer patients. Interact Cardiovasc Thorac Surg 2012; 15: 859–864
  17. Vansteenkiste, et al. 2nd ESMO Consensus Conference on Lung Cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up. Annals of Oncology 25: 1462–1474, 2014
  18. Ung YC, Souter LH, Darling G, Dobranowski J, Donohue L, Leighl N, et al. Follow-up and surveillance of curatively treated lung cancer patients. Toronto (ON): Cancer Care Ontario; 2014 Aug 29. Program in Evidence-Based Care Evidence-Based Series No.: 26-3.

Recommendations for Invasive Mediastinal Staging for Potentially Resectable NSCLC – Choice of Invasive Modality

Indications for Invasive Mediastinal Staging for Potentially Resectable NSCLC

A. When is invasive mediastinal staging indicated?

Background:

As a general rule, invasive staging is typically held to be indicated when the risk of mediastinal lymph node involvement is 10% or greater. There is significant agreement in the existing published guidelines based on moderate to high quality evidence for the following recommendations.

Recommendation

Invasive mediastinal staging is indicated in patients with:

  • Primary tumour >/= 3cm 1-15
  • Central tumour* 1-3, 7, 13, 16-19
  • CT evidence of enlarged N1/N2/N3 nodes 1, 2, 5, 10, 16, 17, 20-23
  • PET evidence of avid N1/N2/N3 nodes 1, 2, 5, 16, 17, 22-25

Note:   Emerging evidence in smaller series has also identified other factors that are associated with an increased risk of mediastinal lymph node involvement. It is not well established if the risk is high enough to justify invasive staging on the basis of these risk factors alone in the absence of the above indications. These additional factors may supplement decision making on a case by case basis:

  • Adenocarcinoma histology 3, 8, 13, 20, 27-29
  • High SUVmax of the primary tumour** 5, 12, 13, 30-34
  • Elevated serum CEA***4, 10, 11, 15, 35

*“Central” is inconsistently defined in the literature26. At the minimum, tumours within the central 1/3 of the chest should undergo invasive staging.
**The threshold value of SUVmax associated with increased risk varies between studies and is poorly defined.
***This test is not a routine part of the work-up of lung cancer in North America

Suggested Reading

  1. Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e211S-50S.
  2. Ettinger DS, Wood DE, Aisner DL, et al. NCCN clinical practice guidelines in oncology. Non-small cell lung cancer. Version 4.2018. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf Accessed June 4, 2018.
  3. de Leyn P, Dooms C, Kuzdzal J, et al. Revised ESTS guidelines for preoperative mediastinal staging for non-small-cell lung cancer. Eur J Cardiothorac Sur. 2014;45:787-98.
  4. Darling G, Dickie A, Malthaner R, Kennedy E, Tey R. Invasive mediastinal staging of non-small-cell lung cancer: A clinical practice guideline. Curr Oncol. 2011;18:e304-9.

References

  1. Ettinger DS, Wood DE, Aisner DL, et al. NCCN clinical practice guidelines in oncology. Non-small cell lung cancer. Version 4.2018. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf Accessed June 4, 2018.
  2. Darling G, Dickie A, Malthaner R, Kennedy E, Tey R. Invasive mediastinal staging of non-small-cell lung cancer: A clinical practice guideline. Curr Oncol. 2011;18:e304-9.
  3. ­Chen K, Yang F, Jiang G, Li J, Wang J. Development and validation of a clinical prediction model for N2 lymph node metastasis in non-small cell lung cancer. Ann Thorac Surg. 2013;96:1761-8.
  4. Cho S, Song IH, Yang HC, Kim K, Jheon S. Predictive factors for node metastasis in patients with clinical stage I non-small cell lung cancer. Ann Thorac Surg. 2013;96:239-46.
  5. Farjah F, Lou F, SIma C, Rusch V, Rizk N. A prediction model for pathologic N2 disease in lung cancer patients with a negative mediastinum by positron emission tomorgraphy. J Thorac Oncol. 2013;8:1170-80.
  6. Fernandez FG, Kozower BD, Crabtree TD, et al. Utility of mediastinoscopy in clinical stage I lung cancers at risk for occult mediastinal nodal metastases. J Thorac Cardiovasc Surg. 2014;149:35-42.
  7. Gao SJ, Kim AW, Puchalski JT, et al. Indications for invasive mediastinal staging in patients with early non-small cell lung cancer staged with PET-CT. Lung Cancer. 2017;109:36-41.
  8. Gomez-Caro A, Boada M, Cabanas M, et al. False-negative rate after positron emission tomography/computer tomography scan for mediastinal staging in c) stage non-small-cell lung cancer. Eur J Cardiothorac Surg. 2012;42:93-100.
  9. Kanzaki R, Higashiyama M, Fujiwara A, et al. Occult mediastinal lymph node metastasis in NSCLC patients diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT: Risk factors, pattern and histopathological study. Lung Cancer. 2011;71:333-7.
  10. Kimura H, Iwai N, Ando S, et al. A prospective study of indications for mediastinoscopy in lung cancer with CT findings, tumor size, and tumor markers. Ann Thorac Surg. 2003;75:1734-9.
  11. Koike T, Koike T, Yamato Y, Yoshia K, Tohabe SI. Predictive risk factors for mediastinal lymph node metastases in clinical stage IA non-small-cell lung cancer patients. J Thorac Oncol. 2012;7:1246-51.
  12. Li L, Ren S, Zhang Y, et al. Risk factors for predicting the occult nodal metastasis in T1-2N0M0 NSCLC patients staged by PET/CT: Potential value in the clinic. Lung Cancer. 2013;81:213-7.
  13. Lee PC, Port JL, Korst RJ, et al. Risk factors for occult mediastinal metastases in clinical stage I non-small cell lung cancer. Ann Thorac Surg. 2007;84:177-81.
  14. Park HK, Jeon K, Koh WJ, et al. Occult nodal metastasis in patients with non-small cell lung cancer at clinical stage IA by PET/CT. Respir. 2010;15:1179-84.
  15. Suzuki K, Nagai K, Yoshida J, et al. Clinical predictors of N2 disease in the setting of a negative computed tomographic scan in patients with lung cancer. J Thorac Cardiovasc Surg. 1999;117:593-8.
  16. Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e211S-50S.
  17. de Leyn P, Dooms C, Kuzdzal J, et al. Revised ESTS guidelines for preoperative mediastinal staging for non-small-cell lung cancer. Eur J Cardiothorac Sur. 2014;45:787-98.
  18. Al-Sarraf N, Aziz R, Gately K, et al. Pattern and predictors of occult mediastinal lymph node involvement in non-small cell lung cancer patients with negative mediastinal uptake on positron emission tomography. Eur J Cardiothorac Surg. 2012;144:1360-4.
  19. Zhang Y, Sun Y, Xiang J, et al. A prediction model for N2 disease in T1 non-small cell lung cancer. J Thorac Cardiovasc Surg. 2012;144:1360-4.
  20. Fibla JJ, Molins L, Simon C, Perez J, Vidal G. The yield of mediastinoscopy with respect to lymph node size, cell type, and the location of the primary tumor. J Thorac Oncol. 2006;1:430-3.
  21. Gurses A, Turna A, Bedirhan MA, et al. The value of mediastinoscopy in preoperative evaluation of mediastinal involvement in non-small-cell lung cancer patients with clinical N0 disease. J Thorac Cardiovasc Surg. 2002;50:174-7.
  22. Pozo-Rodriguez F, Martin de Nicolás JL, Sánchez-Nistal MA, et al. Accuracy of helical computed tomography at [18F] fluorodeoxyglucose positron emission tomography for identifying lymph node mediastinal metastases in potentially resectable non-small-cell lung cancer. J Clin Oncol. 2005;23:8348-56.
  23. Wang L, Jian W, Zhang C, et al. Lymph node metastasis in clinical stage IA peripheral lung cancer. Lung Cancer. 2015;90:41-6.
  24. Yap KK, Yap KS, Byrne AJ, et al. Positron emission tomography with selected mediastinoscopy compared to routine mediastinoscopy offers cost and clinical outcome benefits for pre-operative staging of non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2005;32:1033-40.
  25. Billé A, Pelosi E, Skanjeti A, et al. Preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer: accuracy of integrated positron emission tomography and computed tomography. Eur J Cardiothorac Surg. 2009:36:440-5.
  26. Casal RF, Vial MR, Miller R, et al. What exactly is a centrally located lung tumor? Results of an online survey. Ann Am Thorac Soc. 2017;14:118-23.
  27. Billé A, Okiror L, Skanjeti A, et al. Evaluation of integrated positron emission tomography and computed tomography accuracy in detecting lymph node metastasis in patients with adenocarcinoma vs squamous cell carcinoma. Eur J Cardiothorac Surg. 2013;43:574-9.
  28. Choi YS, Shim YM, Kim J, Kim K. Mediastinoscopy in patients with clinical stage I non-small cell lung cancer. Ann Thorac Surg. 2003;73-364-6.
  29. Mizuno T, Arimura T, Kuroda H, et al. Histological type predicts mediastinal metastasis and surgical outcome in resected cN1 non-small cell lung cancer. Gen Thorac Cardiovasc Surg. 20017;65:519-26.
  30. Cerfolio RJ, Bryant AS, Eloubeidi MA. Routine mediastinoscopy and esophageal ultrasound fine-needle aspiration in patients with non-small cell lung cancer who are clinically N2 negative: A prospective study. Chest. 2006;130:1791-5.
  31. Cerfolio RJ, Bryant AS, Ohja B, Bartolucci AA. The maximum standardized uptake values on positron emission tomography of a non-small cell lung cancer predict stage, recurrence, and survival. J Thorac Cardiovasc Surg. 2005;13-:151-9
  32. Li M, Liu N, Hu M, et al. Relationship between primary tumor fluorodeoxyglucose uptake and nodal or distant metastases at presentation in T1 stage non-small cell lung cancer. Lung Cancer. 2009;63:383-6.
  33. Lin JT, Yang XN, Zhing WZ, et al. Association of maximum standardized uptake value with mediastinal lymph node metastases in cN0 non-small cell lung cancer. Eur J Cardiothorac Surg. 2016;50:914-9.
  34. Miyasaka Y, Suzuki K, Tamakochi K, Matsunaga T, Oh S. The maximum standardized uptake value of fluorodeoxyglucose positron emission tomography of the primary tumour is a good predictor of pathological nodal involvement in clinical N0 non-small-cell lung cancer. Eur J Cardiothorac Surg. 2013;44:83-7.
  35. Ye B, Cheng M, Li W, et al. Predictive factors for lymph node metastasis in clinical stage IA lung adenocarcinoma. Ann Thorac Surg. 2014;98:217-23.
Choice of Invasive Modality

B. Choice of invasive modality

Background

When invasive mediastinal staging is required. Various modalities maybe utilized including, but not limited to cervical mediastinoscopy (CM), endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS). This set of recommendations will compare these techniques and attempt to set some parameters regarding required nodal stations. In doing so, we are very cognizant of the variation in the technology and expertise available at the various Thoracic Surgery centres across the country.

Recommendations

  1. Both cervical mediastinoscopy (CM) and needle (FNA) techniques (EBUS with or without EUS) have excellent reported sensitivity, negative predictive value and accuracy.

Initial reports on the accuracy of EBUS and EUS in lung cancer staging yielded disappointing results with unacceptably high false negative rates. However, more contemporary reports have shown equivalence. Indeed, with wider access to mediastinal lymph node staging, needle techniques may prove to be superior to conventional surgical staging. Combined EBUS and EUS, for example, affords access at lymph nodes from station 2R, 2L, 3p, 4R, 4L, 5, 6, 7, 8R, 8L, 9R, 9L, 10R, 10L, 11R and 11L.

  1. We recommend that invasive mediastinal staging, whether with mediastinoscopy or needle techniques should include sampling of at least the right paratracheal lymph node station (station 4R), left paratracheal lymph node station (station 4L) and subcarinal lymph node (station 7), as well as any other suspicious lymph node station by CT or PET criteria

Conventional reports of adequate mediastinoscopy in invasive staging of the mediastinum stipulate that both lower paratracheal lymph node stations and the subcarinal lymph node station should be sampled. While there may not be a lot of evidence that support this convention, it does seem like a reasonable and valid recommendation. This same rule should apply to needle techniques for the same reasons. Therefore, regardless of procedure, an invasive mediastinal staging procedure should only be considered adequate if it samples lymphoid tissue from both lower paratracheal lymph nodes and subcarinal lymph node, and any lymph nodes that are considered suspicions by CT or PET. For example, in a patient with a right upper lobe tumor and a suspicious high paratracheal lymph node by PET, and adequate mediastinoscopy or EBUS would include lymphoid tissue sampled from at least stations 4R, 4L, 7 and 2R.

  1. If both procedures are readily available at an institution, then needle techniques (preferably under sedation in an endoscopy suite) should preferentially be selected to cervical mediastinoscopy

The most important factors in selecting which procedure to use is whether the selected procedure is performed adequately with good results, and whether the target lymph nodes are within reach of that procedure. For example, using mediastinoscopy alone in a patient with left lower lobe tumor and a suspicious lower paraesophageal lymph node (station 8L) would not be considered adequate even if lymph node tissue is adequately obtained from stations 4R, 4L and 7. However, in situations where both procedures can be used safely and adequately, the panel recommends a needle technique. This is because of the lower incidence of devastating complications and the lower cost associated with needle techniques. One should note, that the cost advantage of needle techniques is more pronounced when they are performed in an endoscopy suite.

  1. In an institution where needle techniques are available with high quality, there is no need to confirm negative results with a more invasive procedure.

Given the equivalent results obtained by both procedures in the right setting, the practice of routinely confirming negative EBUS or EUS resulted is not supported by the current literature and is not necessary. There are situations where a negative EBUS or EUS result may require confirmation with a more invasive technique, such as CM or thoracoscopy. This includes inadequate samples or highly suspicious lymph nodes by imaging criteria that are unexpectedly negative.

Suggested reading

  1. Silvestri GA, Gonzalez AV, Jantz MA, Margolis ML, Gould MK, Tanoue LT, Harris LJ, Detterbeck FC. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May;143(5 Suppl):e211S-e250S
  2. Yasufuku K, Pierre A, Darling G, de Perrot M, Waddell T, Johnston M, da Cunha Santos G, Geddie W, Boerner S, Le LW, Keshavjee S. A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediastinal lymph node staging of lung cancer. J Thorac Cardiovasc Surg. 2011 Dec;142(6): 1393-400
  3. Liberman M, Sampalis J, Duranceau A, Thiffault V, Hadjeres R, Ferraro P. Endosonographic mediastinal lymph node staging of lung cancer. Chest. 2014 Aug;146(2):389-397
  4. Czarnecka-Kujawa K, Rochau U, Siebert U, Atenafu E, Darling G, Waddell TK, Pierre A, De Perrot M, Cypel M, Keshavjee S, Yasufuku K. Cost-effectiveness of mediastinal lymph node staging in non-small cell lung cancer. J Thorac Cardiovasc Surg. 2017 Jun;153(6):1567-1578
  5. Nasir BS, Yasufuku K, Liberman M. When should negative endobronchial ultrasound findings be confirmed by a more invasive procedure? Ann Surg Oncol. 2018 Jan;25(1):68-75

Lung Cancer Screening.


Background:

The positions and recommendations herein should be regarded as the product of a non-systematic literature review. They are however in accordance (with some specific societal variations) with the positions advocated by the Canadian Task Force on Preventive Health Care, the US Preventive Services Task Force, the American College of Chest Physicians, The American Cancer Society, the American Association of Thoracic Surgery and the National Comprehensive Cancer Network. Our hope is that this recommendation is of utility to CATS members and other stakeholders including our patient community.

Notes:

  1. There is one large-scale, well powered RCT, several smaller RCTs and a number of institutional series to consider.
  2. The existing randomized trials produce conflicting conclusions regarding the benefit or absence of benefit to lung cancer screening.
  3. A large number of professional societies, task-forces and governing bodies have published formal position statements on lung cancer screening, and in particular the Canadian Task Force on Preventive Health has adopted a stance on this issue and is in favor of lung cancer screening.
  4. The primary study, which drives the general support in favor of lung cancer screening from most societies and task forces, is the National Lung Screening Trial (NLST)
  5. The NLST was a randomized trial comparing annual screening low-dose CT (LDCT) vs CXR for 3-years in >53,000 patients in the US. The study targeted “high-risk” patients with inclusion criteria being: i) men and women 55-74 years of age ii) history of at least 30 pack-years smoking (current or those who quit within 15 years of enrollment)
    1. Key Findings:
      1. A positive finding was that of a non-calcified nodule >4mm. 39% of LDCT screened patients had at least one positive scan
      2. 96.4% of positive scans were false-positive scans, and follow up was at discretion of the institution
      3. 90% of positive scans led to a further investigation
      4. The rate of adverse events from interventions for positive scans was low at 1.4% of LDCT patients
      5. There were 247 lung cancer deaths per 100,000 person-years in the LDCT group and 309 lung cancer deaths per 100,000 person-years in the CXR group
      6. This translates into a relative reduction in lung cancer mortality of 20%, and a relative reduction in all-cause mortality of 6.7%
      7. This translates to the need to screen 320 persons annually for 3-years to prevent one lung cancer death over six years.
  6. CXR alone does not reduce mortality for lung cancer and is not recommended as a screening modality
  7. LDCT is more sensitive than CXR in detecting small asymptomatic lung cancers
  8. Screening has a high false positive rate, and leads to a large volume of additional investigations including further imaging and some invasive procedures
  9. Participation in a screen trial was associated with a favorable reduction in smoking cessation
  10. The concern of cost-effectiveness associated with screening is a major issue. Modelling studies suggest LDCT screening may reduce lung cancer mortality over 10 years at a cost of $81,0002 – 269,0003 per quality-adjusted life years.
  11. Screening for lung cancer cannot be thought of as a single intervention and requires a dedicated program that involves knowledgeable counselling, discussion of potential risks, expert radiology, thoracic surgery and pathology, and resources to ensure follow up and management of incidental findings
  12. Smoking cessation is a more effective and more cost-effective intervention to reduce lung cancer mortality than is screening.

Recommendation

CATS acknowledges that the provision of clinical care, and the associated resources required to implement a potential lung cancer screening program are considerable, and ultimately may not be possible in each jurisdiction.

It is Only within the confines of a dedicated lung cancer screening program, CATS recommends screening asymptomatic adults aged 55 to 74 years, who are in good health, with at least a 30 pack-year smoking history who smoke or have quit smoking within 15 years, with low-dose, non-contrast CT scanning of the chest, every year for three consecutive years. At this time CATS cannot provide a recommendation of subsequent screening following this 3-year interval.

Key References

1.Reduced lung-cancer mortality with low-dose computed tomography screening. NEJM. 2011;365(5):395.
2.Cost-effectivenes of CT screening in the National Lung Screening Trial. NEJM 2014 Nov;371(19):1793-802
3.Cost-effectiveness of computed tomography screening for lung cancer in the United States. J Thorac Oncol. 2011;6(11):1841.