[Delphi Expert Consensus of the German Society for Thoracic Surgery on Segmentectomy for Non-small Cell Lung Cancer]. / Delphi-Experten-Konsens der Deutschen Gesellschaft für Thoraxchirurgie über die anatomische Segmentresektion bei nicht kleinzelligem Lungenkarzinom.

BACKGROUND: Findings from two recently published randomised controlled trials have shown favourable oncological results of segmentectomy for early-stage NSCLC < 2 cm. This has generated a growing interest in this procedure, which is however considered technically more challenging than lobectomy. The aim of the working group of the German Society for Thoracic Surgery (DGT) was to address, via an expert consensus project, topics concerning implementation of segmentectomy in lung cancer surgery. METHODS: The assigned group of the DGT designed and conducted two electronic rounds of questions in all major thoracic and lung cancer centres in Germany. The steering group predefined a priori the threshold of consensus of 75% or greater. The results were discussed in an expert meeting, leading to a final Delphi poll for selected topics and questions. RESULTS: Thirty-eight questions on segmentectomy for NSCLC were proposed in two rounds and voted on. After the final Delphi process, a consensus was reached for the following topics: non-inferiority of segmentectomy vs. lobectomy for tumours < 2 cm, segmentectomy as an alternative if lobectomy is functionally not feasible, use of intraoperative techniques for identification of intersegmental borders. No consensus could be reached for topics such as frozen section for intraoperative ascertainment of radicality, as also for the indication of a re-do lobectomy in case of an occult N1 lymph node status. CONCLUSION: Our manuscript depicts the results of a Delphi process in 2020/2021 involving experts of the German Society for Thoracic Surgery on the implementation of segmentectomy in lung cancer patients. In general, a very high rate of consensus was documented for the majority of the topics concerning the indication and execution of lung segmentectomy.

Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA(N2) and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy (ESPATUE).

PURPOSE: Concurrent chemoradiotherapy with or without surgery are options for stage IIIA(N2) non-small-cell lung cancer. Our previous phase II study had shown the efficacy of induction chemotherapy followed by chemoradiotherapy and surgery in patients with IIIA(N2) disease and with selected IIIB disease. Here, we compared surgery with definitive chemoradiotherapy in resectable stage III disease after induction. PATIENTS AND METHODS: Patients with pathologically proven IIIA(N2) and selected patients with IIIB disease that had medical/functional operability received induction chemotherapy, which consisted of three cycles of cisplatin 50 mg/m(2) on days 1 and 8 and paclitaxel 175 mg/m(2) on day 1 every 21 days, as well as concurrent chemoradiotherapy to 45 Gy given as 1.5 Gy twice daily, concurrent cisplatin 50 mg/m(2) on days 2 and 9, and concurrent vinorelbine 20 mg/m(2) on days 2 and 9. Those patients whose tumors were reevaluated and deemed resectable in the last week of radiotherapy were randomly assigned to receive a chemoradiotherapy boost that was risk adapted to between 65 and 71 Gy in arm A or to undergo surgery (arm B). The primary end point was overall survival (OS). RESULTS: After 246 of 500 planned patients were enrolled, the trial was closed after the second scheduled interim analysis because of slow accrual and the end of funding, which left the study underpowered relative to its primary study end point. Seventy-five patients had stage IIIA disease and 171 had stage IIIB disease according to the Union for International Cancer Control TNM classification, sixth edition. The median age was 59 years (range, 33 to 74 years). After induction, 161 (65.4%) of 246 patients with resectable tumors were randomly assigned; strata were tumor-node group, prophylactic cranial irradiation policy, and region. Patient characteristics were balanced between arms, in which 81 were assigned to surgery and 80 were assigned to a chemoradiotherapy boost. In arm B, 81% underwent R0 resection. With a median follow-up after random assignment of 78 months, 5-year OS and progression-free survival (PFS) did not differ between arms. Results were OS rates of 44% for arm B and 40% for arm A (log-rank P = .34) and PFS rates of 32% for arm B and 35% for arm A (log-rank P = .75). OS at 5 years was 34.1% (95% CI, 27.6% to 40.8%) in all 246 patients, and 216 patients (87.8%) received definitive local treatment. CONCLUSION: The 5-year OS and PFS rates in randomly assigned patients with resectable stage III non-small-cell lung cancer were excellent with both treatments. Both are acceptable strategies for this good-prognosis group.

Does dose matter? Effect of two different neoadjuvant protocols in advanced NSCLC.

BACKGROUND: For stage III, NSCLC neoadjuvant protocols have been intensified up to full dose protocols but up till now the effect of more intensive protocols in a trimodal setting could not be compared directly because of different selection criteria or experience of involved facilities in different studies or multicenter studies. We analyzed our experience with two different neoadjuvant protocols, consistent selection criteria, and surgical teams over 17-year time period. METHOD: Single-center retrospective study in 159 patients concerning survival, recurrence, and downstaging effect. RESULTS: Overall median survival was 32 months, with 26 months for protocol 1, and 35 months for protocol 2, respectively. Hospital mortality was 5%. Log-rank test showed significant difference between the protocols for UICC-downstaging-effect, ypT-stage, ypN-stage, and ypUICC-stage, respectively, but only ypN-stage and ypUICC-stage were significant risk factors for survival using Cox regression. CONCLUSION: The median survival benefit of 9 months is evident but (probably still) not significant. The more aggressive protocol 2 shows a significant better downstaging effect concerning N- and UICC-stage if R0-resection can be achieved. Insofar dose does matter!

Surgery on unfavourable persistent N2/N3 non-small-cell lung cancer after trimodal therapy: do the results justify the risk?

OBJECTIVES: Persistent mediastinal lymph node metastasis after neoadjuvant therapy is a significant negative indicator for survival. Even though there is still no consensus on the matter, some authors advocate a thorough restaging prior to surgery and deny surgery in cases of persistent N2 because of the poor outcome. We analysed our results after trimodal therapy in pN2/N3 stage III non-small-cell lung cancer (NSCLC) and persistent mediastinal lymph node metastasis after neoadjuvant chemoradiotherapy. METHODS: We conducted a retrospective cohort analysis of 167 patients who received trimodal therapy for stage III NSCLC. Progression-free interval and survival were calculated. T-stage, N-stage, ypT-stage, ypN2/3-stage and surgical procedure were tested as risk factors. RESULTS: Eighty-three patients with potentially resectable initial pN2/3 underwent 44 pneumonectomies and 76% extended resections. Thirty-five patients showed persistent mediastinal lymph node metastasis after trimodal therapy. Treatment-related comorbidity after an operative therapy was 58%. Hospital mortality was 2.4%. The ypT- and ypN2/N3 stages were significant risk factors and, in the case of persistent mediastinal lymph node metastasis, median progression-free period was 17 months and median survival time was 21 months. CONCLUSIONS: Persistent but resectable N2/N3 after chemoradiotherapy in stage III NSCLC is the least favourable subgroup of patients in neoadjuvant approaches. If surgery can be carried out with curative intent and low morbidity, completing trimodal therapy is justified, with an acceptable outcome.

Pneumonectomy: calculable or non-tolerable risk factor in trimodal therapy for Stage III non-small-cell lung cancer?

OBJECTIVES: Lung cancer is the leading cause of death in cancer statistics throughout developed countries. While single surgical approach provides best results in early stages, multimodality approaches have been employed in advanced disease and demonstrated superior results in selected patients. With either full-dose chemotherapy and/or radiotherapy, patients usually have a poor general condition when entering surgical therapy and therefore neoadjuvant therapy can lead to a higher morbidity and mortality. Especially in the case of pneumonectomy as the completing procedure, mortality rate can exceed over 40%. Therefore, chest physicians often shy away from recommending pneumonectomy as final step in trimodal protocols. We analysed our experience with pneumonectomy after neoadjuvant chemoradiotherapy in advanced non-small-cell lung cancer (NSCLC) with a focus on feasibility, outcome and survival. METHODS: Retrospective, single-centre study of 146 patients with trimodal neoadjuvant therapy for NSCLC Stage III over 17 years time span. Follow-up was taken from our own outpatient files and with survival check of central registry office in Baden-Württemberg, Germany. RESULTS: A total of 118 men and 28 women received 62 lobectomies, 6 bi-lobectomies and 78 pneumonectomies after two different neoadjuvant protocols for Stage III NSCLC. Overall morbidity rate was 53 and 56% after pneumonectomy. Overall hospital mortality rate was 4.8 and 6.4% after pneumonectomy. Overall median survival rate was 31 months with a 5-year survival rate of 38% (Kaplan-Meier). Pneumonectomy, right-sited pneumonectomy and initial T- and N-stages were no risk factors for survival (log-rank test). Significant factors for survival were ypT-stage, ypN-stage, yUICC-stage in univariate testing (log-rank test) and ypUICC-stage in multivariate testing (Cox's regression). CONCLUSIONS: Pneumonectomy in neoadjuvant trimodal approach for Stage III NSCLC can be done safe with acceptable mortality rate. Patients should not withhold from operation because of necessitating pneumonectomy. Not the procedure but the selection, response rate and R0-resection are crucial for survival after trimodal therapy in experienced centres.

Phase II trial of a trimodality regimen for stage III non-small-cell lung cancer using chemotherapy as induction treatment with concurrent hyperfractionated chemoradiation with carboplatin and paclitaxel followed by subsequent resection: a single-center study.

PURPOSE We started a phase II trial of induction chemotherapy and concurrent hyperfractionated chemoradiotherapy followed by either surgery or boost chemoradiotherapy in patients with advanced, stage III disease. The purpose is to achieve better survival in the surgery group with minimum morbidity and mortality. PATIENTS AND METHODS Patients treated from 1998 to 2002 with neoadjuvant chemoradiotherapy and surgical resection for stage III NSCLC were analyzed. The treatment consisted of four cycles of induction chemotherapy with carboplatin/paclitaxel followed by chemoradiotherapy with a reduced dose of carboplatin/paclitaxel and accelerated hyperfractionated radiotherapy with 1.5 Gy twice daily up to 45 Gy. After restaging, operable patients underwent thoracotomy. Inoperable patients received chemoradiotherapy up to 63 Gy. Study end points included resectability, pathologic response, and survival. Results One hundred twenty patients were enrolled; 25% patients had stage IIIA, 73% had stage IIIB, and 2% stage IV. After treatment, 47.5% had downstaging, 29.2% had stable disease, and 23.3% had progressive disease. Thirty patients (25%) were not eligible for operation because of progressive disease, stable disease, and/or functional deterioration with one treatment-related death. The 30-day mortality was 5% in patients who underwent operation. The 5-year survival rate for 120 patients was 21.7%, and it was 43.1% in patients with complete resection. In postoperative patients with stage N0 disease, 5-year survival was 53.3%; if stage N2 or N3 disease was still present, 5-year survival was 33.3%. CONCLUSION Staging and treatment with chemoradiotherapy and complete resection performed in experienced centers achieve acceptable morbidity and mortality.

Impact of neo-adjuvant radiochemotherapy on bronchial tissue viability.

OBJECTIVE: In the treatment of advanced stages of lung cancer, increasingly more multimodality approaches applying radiotherapy and/or chemotherapy in a neo-adjuvant setting are being introduced. The impact of induction therapy, especially radiotherapy, on bronchial tissue viability has not been investigated so far. METHODS: In 2008, we determined the tissue viability of bronchial segments obtained during surgery in 45 consecutive patients, including patients after neo-adjuvant radiochemotherapy (RCTX). Bronchial tissue viability was analysed by histology, life-dead assay and cell proliferation in tissue-specific culture media. Biomedical findings were compared with the clinical course of the patients. RESULTS: Tissue samples of 44 patients were included into this study. Fourteen patients (32%) had undergone neo-adjuvant RCTX. Histology and life-dead assay of the bronchial segments did not show significant differences. While patient age, sex, tumour entity and site of resection had no influence on cell proliferation in vitro, previous RCTX resulted in a 46% decrease of bronchial tissue viability (P=0.01). However, this effect was not reflected by the clinical course of the operated patients. CONCLUSIONS: Neo-adjuvant RCTX reduces bronchial tissue viability substantially. However, this impairment does not necessarily translate into an increased rate of postoperative bronchial insufficiencies. Standard histological work-up is not sensitive enough to characterise changes in bronchial tissue viability following RCTX.

Trimodal therapy for histologically proven N2/3 non-small cell lung cancer: mid-term results and indicators for survival.

BACKGROUND: Surgery alone for stage III non-small cell lung cancer provides a 5-year survival of 20% and competes with multimodal treatments. In 1999, a trimodal protocol was implemented at the Schillerhöhe Clinic. The aim of this study was to verify the feasibility and outcome of this trimodal protocol including survival, risk factors for survival, and comorbidity in a single institution. METHODS: Included were all patients with potentially resectable, previously untreated stage III non-small cell lung cancer operated on between February 1999 and May 2006 in the General Thoracic Surgery Unit of the Schillerhöhe Clinic following the same neoadjuvant protocol. Treatment-related morbidity, recurrence, survival after R0 resection, and risk factors for survival (pN0 after trimodal therapy, downstaging of International Union Against Cancer stage, T downstaging, N downstaging, regression rate, and histologic type of tumor) were analyzed. RESULTS: From 107 patients with stage III non-small cell lung cancer, 55 patients with mediastinoscopy-positive N2 or N3 were eligible for this study. Forty patients (72%) had the effect of International Union Against Cancer downstaging. Treatment-related comorbidity was 54% with hospital and 120-day mortality of 3.6% and 5.4%, respectively. Overall mean survival (Kaplan-Meier) was 43 months (95% confidence interval, 35 to 52) with an estimated 5-year survival rate of 49%. In multivariate testing, International Union Against Cancer downstaging after trimodal therapy achieved a level of significance (p = 0.031), and patients with UICC-downstaging after trimodal therapy had a mean survival of 53 months (95% confidence interval, 44 to 63) with an estimated 5-year survival rate of 60%. CONCLUSIONS: Neoadjuvant trimodal treatment for histologically proven N2 or N3 stage III non-small cell lung cancer is promising and can, like no other approach at present time, considerably improve 5-year survival rates up to 63% in selected patients.

Long-term efficiency of endoscopic thoracic sympathicotomy: survey 10 years after surgery.

Immediate and short-term results of endoscopic thoracic sympathectomy (ETS) for primary hyperhidrosis are good. Adverse effects have been identified clearly and are supposed to decrease with time. In this institutional report, the long-term results of ETS with regard to efficacy, side effects and patient satisfaction are presented. Fifteen patients were included and mean follow-up time was 12+/-2 years. ETS success rate, rate of compensatory sweating and degree of patient satisfaction were assessed. We detected 8 patients (53%) complaining about a decent to moderate recurrence of hand sweating and compensatory and gustatory sweating were observed in 9 (60%) and 5 (33%) patients, respectively. Reported side effects related to surgery were paresthesias of the upper limb and the thoracic wall in 8 patients (53%) and recurrent pain in the axillary region in one. At an average 12 years after surgery, 47% of patients were satisfied with the treatment results, 40% were disappointed. Six patients (40%) affirmed they would ask for the operation if it were to be redone. Our findings indicate that results of ETS deteriorate and compensatory sweating does not improve with time. It is mandatory to inform patients of the potential long-term adverse effects before surgery.

Full-thickness resection with myocutaneous flap reconstruction for locally recurrent breast cancer.

BACKGROUND: Despite available recommendations, therapeutic procedures of locally recurrent breast cancer are very different. This retrospective study presents the possibilities and results of complete, full-thickness chest wall resection. METHODS: Between 1985 and 2006, 63 women (mean age, 58 years) with local recurrence of breast cancer invading the chest wall underwent chest wall resection with myocutaneous flap coverage and are included in this study. Adequate lung, cardiovascular, renal, and hepatic functions were additional eligibility requirements for inclusion. Preoperative known extrapulmonary metastases, pleural dissemination, and Eastern Cooperative Oncology Group (ECOG) status 3 or 4 were exclusion criteria. Survival rates were calculated by the Kaplan-Meier method. Univariable and multivariable Cox regression analysis was used for relative risk factors. RESULTS: The median interval between operation for the primary tumor and of the local recurrence was 89 months, with median follow-up at 28 months. In the total collective, cumulative 5-, 10- and 15-year survival rates were 46%, 29%, and 22%, respectively, with a median survival of 56 months. R0 resection was associated with a 5-year survival of 50.4%. Prognostic factors were patient age at the time of the primary operation and tumor invasion of bony structures. Mortality was 1.6% and morbidity was 25%. CONCLUSIONS: Full-thickness chest wall resection of locally recurrent breast cancer performed by a team of thoracic and plastic surgeons provides the best survival rates, with low mortality and morbidity. An earlier application of this method may lead to further improvement of these results.

Carcinoid lung tumors: long-term results from 111 resections.

OBJECTIVE: Carcinoids are rare neuroendocrine tumors of the bronchial system. Only recently, the histological classification was standardized, and there are varying opinions about the extent of surgical resection. This research reports on the long-term results of 111 consecutive patients, who underwent surgery in a department for thoracic surgery. METHODS: Between 1/1988 and 2/2001, 111 consecutive pulmonary resections were conducted in patients with bronchial carcinoids. Retrospectively, researchers obtained clinical and surgical data and re-classified all histological specimen according to the WHO classification of 1999. Information regarding long-term results was obtained by using data obtained during follow-up visits and by talking to the patient on the phone. RESULTS: 97 patients with typical and 14 with atypical carcinoids were identified. The preoperative diagnosis of typical or atypical carcinoid had been correct in 56 patients (50.5%). Surgical procedures included 79 lobectomies, 16 bilobectomies, 8 pneumonectomies, 5 segmental resections, 2 sleeve resections of the main bronchus without parenchymal resection and one exploratory thoracotomy. Mediastinal lymphadenectomies were performed on 105 patients (94.6%). Postoperative staging revealed 91 patients (81.2%) in UICC stage I, 12 (10.8%) in stage II, 7 in stage III and one in stage IV. 97 (87.4%) typical and 14 (12.6%) atypical carcinoids were classified. 30-day mortality was 1.8% (n=2). Mean follow-up was 73.4 months. The total cohort showed a 5-year survival rate of 94% and a 10-year survival rate of 82%. In patients with typical and atypical carcinoids, the 5-year survival rates were 94% and 82%, respectively (n.s.), and the 10-year survival rates were 92% and 62%, respectively (p<0.01). The 5- (10-) year survival rate without lymph node involvement was 96% (85%), with N1 involvement 88% (65%), with N2 involvement 67% (no 10-year survival). CONCLUSIONS: Patients with bronchial carcinoids who underwent a radical oncological resection with mediastinal lymphadenectomy have very good survival chances. There are no prospective randomized studies evaluating the surgical procedures as they relate to the classification. Since a preoperative diagnosis cannot clearly determine if the lymph nodes are involved and what histology type the physician dealing with, a limited resections without lymphadenectomy is insufficient. It is absolutely necessary to conduct retrospective and multi-center studies on the prognostic importance of lymph node involvement and on the impact of adjuvant therapies.

Full-thickness chest wall resection for locally recurrent breast cancer.

AIM: In spite of available recommendations, therapeutic procedures of locally recurrent breast cancer are very different. In a retrospective study, the possibilities and results of complete, full-thickness chest wall resection are presented. METHODS: Between 1985 and 2004, 51 women underwent complete, full-thickness chest wall resection with primary coverage. Primary surgical therapy of breast cancer had been mastectomy in 88%. Median age of patients undergoing surgery for a local recurrence was 57 (29 - 81) years. The median interval between surgery of the primary tumour and of the local recurrence was 70.3 (10.7 - 327.2) months; median follow-up was 29.4 (1.8 - 230.9) months. 40 (78.4%) patients required rib resections, 15 (29.4%) of them in combination with partial sternal resection. In 4 (7.8%) patients complete and in 7 (13.7%) patients partial sternal resection without additional rib resection were performed.Coverage was mainly realized using latissimus dorsi myocutaneous flaps (n=44; 86.3%). Survival rates were calculated by means of the Kaplan-Meier method, the relative risk using univariate and multivariate Cox-regression analysis. RESULTS: In the total collective, cumulative 5-, 10- and 15-year survival (YS) rates were 39%, 31% and 23%, respectively, median survival 46.4 months. R0 resection was associated with a 5-YS of 42%. Prognostic factors were age at the time of primary surgery, disease-free interval and tumour invasion of bony structures. Mortality was 2%, morbidity 35%. CONCLUSION: Full-thickness chest wall resection of locally recurrent breast cancer is possible in almost any patient when performed by a team of thoracic and plastic surgeons. Only radical resection provides good long-term results with low mortality and morbidity.