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Neoadjuvant therapy for rectal cancer down-stages the tumor but reduces lymph node harvest significantly.

PURPOSE: The impact of neoadjuvant therapy (NAT) for rectal cancer on lymph node yield is not well known. This study evaluates the impact of NAT on tumor regression and lymph node harvest. METHODS: The subjects were 40 patients with rectal cancer; 20 receiving high-dose, long-course neoadjuvant therapy, and 20 age- and sex-matched controls who did not receive neoadjuvant therapy. Tumor regression (TRG) was graded from 1 to 5 as: TRG1, no residual tumor cells; TRG2, occasional residual tumor cells with marked fibrosis; TRG3, marked fibrosis with scattered tumor cells or groups; TRG4, abundant cancer cells with little fibrosis; TRG5, no tumor regression. We also evaluated the number of lymph nodes retrieved from excised specimens, the size of the largest node, and the extent of lymph node involvement by the tumor. RESULT: Tumor regression was seen in all patients; as TRG1 in 6 (30%), TRG2 in 2 (10%), TRG3 in 3 (15%), and TRG4 in 9 (45%). The median nodal harvest was 4 (range (0-12) in the NAT group vs 9 (range 1-19) in the control (P = 0.001). The median size of the largest lymph node was 5 mm (range 2-12 mm) in the NAT group vs 9 mm (range 4-15 mm) in the control group (P = 0.004). Tumor-positive nodes were identified in 4 of 17 of the NAT group patients and in 9 of the 20 controls (P = 0.308). CONCLUSION: Although NAT down-stages rectal cancer, it results in a significantly low yield of lymph nodes, which are also significantly smaller than those in nonirradiated controls. Therefore, surgeons and histopathologists must ensure adequate sampling and accurate staging is done for patients with irradiated rectal cancer.

Adult↗

[Neoadjuvant therapy for colorectal cancer].

To assess the role of neoadjuvant therapy in the treatment of colorectal cancer, we reviewed the literature investigating the effects of chemotherapy and/or radiotherapy given prior to surgery. Rationales for enteral administration of fluoropyrimidines preoperatively, in terms of pharmacokinetic and antitumor effects, have been demonstrated in clinical studies. For instance, the concentration of 5-FU in cancer tissue was shown to be significantly higher than in normal tissue, and a dose-response relationship between the cumulative doses of the agent and the histological antitumor effect was observed. Among several comparative studies, there were reports suggesting the efficacy of preoperative chemotherapy. The treatment group had a slight, but insignificant, improvement in disease-free interval or long-term survival. On the other hand, some randomized trials for rectal cancer demonstrated that preoperative radiotherapy could decrease local failure, and that patients who underwent curative surgery appeared to have an improved 5-year survival compared to the controls, although overall survival was not improved. Recent reports on combined modality treatment with chemotherapy and radiotherapy clearly showed a downstaging effect on the primary tumor and the decreased prevalence of regional involved lymph node. Further developments through rationally designed study are necessary to ascertain the efficacy of neoadjuvant therapy for colorectal cancer.

Chemotherapy, Adjuvant↗

Neoadjuvant therapy in breast cancer: can we define its role?

It remains unclear whether neoadjuvant therapy increases disease-free survival when compared with an approach in which chemotherapy is delayed until after surgery. However, the current rationale for neoadjuvant therapy is based on its usefulness in quickly evaluating the likely benefit of new approaches to treatment and tailoring therapy to the biological characteristics of the individual tumor. In the primary therapy of breast cancer, the Aberdeen study shows that patients unresponsive to an anthracycline-based neoadjuvant regimen may achieve a response when switched to docetaxel. Further, patients with an initial clinical response to CVAP were more likely to show a pathological complete response (pCR) at final assessment when four cycles of CVAP were followed by four of docetaxel than when CVAP was maintained for eight cycles (pCR rate 34% versus 16%). Early data suggest that this difference translates into significantly lengthened progression-free survival. As in other disease settings, it may be possible to devise nonanthracycline-containing neoadjuvant regimens which are at least as effective as those in current use.

Breast Neoplasms↗

Impact of neoadjuvant therapy on postoperative complications in patients undergoing resection for rectal adenocarcinoma.

Surgical resection continues to be the mainstay of treatment for rectal cancer. Neoadjuvant therapy (chemotherapy and radiation) has also been shown to be efficacious. The impact of preoperative chemotherapy and radiation on postoperative complications is unclear. The purpose of this study is to evaluate the relationship of neoadjuvant therapy on postoperative complications in patients undergoing a resection of rectal cancer. A total of 325 patients who underwent curative resection for rectal cancer from 1984 to 2001 were retrospectively reviewed. Only cases with complete data sets who had undergone surgery at this institution were evaluable (257). The patients were divided into groups based on the operative procedure performed; abdominoperineal resection (APR) versus sphincter-sparing (SS) procedures (LAR/Transanal) and whether or not preoperative chemotherapy or radiation was administered. There was no significant difference between complication rates for APR and SS with 19 per cent and 14 per cent, respectively. The preoperative therapy had no effect on complications after APR. However, the SS group showed 21 per cent of the patients who received radiation had complications compared to 11 per cent in those who did not (P = 0.087). Complications in the SS group included leaks, wound infections, abscess, embolism, cardiac dysrhythmias, and myocardial infarctions. The 30-day mortality was 1.9 per cent for the entire cohort with no clear difference between groups. There was no significant difference in complication rate between APR and SS. In the APR group, neoadjuvant therapy had no impact on the incidence of complications. However, the SS group did show a trend between preoperative chemotherapy and radiation and complication rate. However, this may not outweigh the advantages of preoperative therapy in this setting.

Adenocarcinoma↗

[Histologic response after neoadjuvant therapy in rectal adenocarcinoma: own experience and review of the literature].

BACKGROUND: Neoadjuvant therapy has improved outcomes for patients with locally advanced rectal cancer. AIM AUTHORS: We studied the degree of histopathological regression after radiotherapy regimens commonly used in their clinical practice, and its effect on the pathology of by clinically founded T3-T4 rectal cancer. PATIENT AND METHODS: A total of 57 patients were investigated who underwent neoadjuvant radiotherapy or chemoradiotherapy--commonly used at our institute--for biopsy proven primary mid or lower third rectum adenocarcinoma between January and December 2004. The standard surgical treatment was anterior resection sec Dixon, Lloyd-Davies--and Hartmann's procedure, all with total mesorectal excision. RESULTS: The surgical specimens were examined by selected pathologists and a modified pathologic staging system the Rectal Cancer Regression Grade (RCRG) was used. (I) "good" response (n=12, 21%), (II) "median" response (n=25, 44%), (III) "poor" response (n=20, 35%). Significant tumor regression (RCRG I-II.) was seen in 37 patients (65%). Six patients (10.5%) have had complete pathological regression and 6 patients (10.5%) have had only microscopic foci of adenocarcinoma. CONCLUSION: Comparing of pretreatment and pathologic staging revealed that the depth of invasion was significantly downstaged. The authors also reviewed the literature of neoadjuvant therapy, total mesorectal excision, prognostic and predictive factors of rectal cancer.

Adenocarcinoma↗

Neoadjuvant therapy for adenocarcinoma of the rectum: tumor response and acute toxicity.

PURPOSE: This study was designed to evaluate the down-staging effect and acute toxicity of preoperative radiation and chemoradiation for primary adenocarcinoma of the rectum. METHODS: The results of pretreatment staging with transrectal ultrasound and computed tomography were compared with final histologic stage in 260 consecutive patients who underwent neoadjuvant therapy and proctectomy for primary adenocarcinoma of the rectum. Patients underwent short-course radiation (2,000 cGy in five fractions), long-course radiation (4,500 cGy in 25 fractions), or chemoradiation (4,500 cGy in 25 fractions with concurrent chemotherapy). RESULTS: Down-staging of one or more T stages occurred in 116 of 260 (45 percent) patients overall (short-course radiation 34/82 (42 percent), long-course radiation 55/122 (45 percent), chemoradiation 27/56 (48 percent), P = not significant). Down-staging of one or more N stages occurred in 85 of 178 (48 percent) patients overall (short-course radiation 12/45 (27 percent), long-course radiation 49/86 (57 percent), chemoradiation 24/47 (51 percent), P = 0.003). Complete pathologic response was observed in 16 of 260 (6 percent) patients overall (short-course radiation 4/82 (5 percent), long-course radiation 5/122 (4 percent), chemoradiation 7/56 (13 percent), P = 0.08). Resection with negative margins (distal, proximal, and radial) was achieved in 211 of 227 patients (93 percent) in whom complete radial margin data were available. Permanent stomas were created in 35 percent of patients; temporary stomas were created in 15 percent. Thirty-three Grade 3 or 4 toxicities occurred in 22 of 260 (8 percent) patients overall during neoadjuvant therapy. Toxicity was more frequent in patients receiving chemoradiation (14/56; 25 percent) and long-course radiation (8/122; 7 percent) than in those receiving short-course radiation (0/82; 0 percent), P < 0.0001. Perioperative complications occurred in 93 patients overall (36 percent). The postoperative mortality rate was 0.4 percent (1/260). There was no significant difference in the complication rate between patients treated with short-course radiation (26/82; 32 percent), long-course radiation (46/122; 36 percent), and chemoradiation (21/56; 38 percent). CONCLUSION: Neoadjuvant therapy for adenocarcinoma of the rectum is well tolerated and can produce substantial down-staging and a high curative resection rate. Chemoradiation can achieve high complete pathologic response rates, although toxicity during neoadjuvant therapy is greater than for radiation alone. Short-course radiation can achieve down-staging of both T stage and N stage.

Adenocarcinoma↗

[Apoptosis and tumor regression in locally advanced non-small cell lung cancer with neoadjuvant therapy].

Dysregulation of apoptosis is closely associated with malignant cell transformation. On the other hand, apoptosis is induced by chemotherapy or irradiation. Therefore, in 54 patients with locally advanced non-small cell lung cancer (NSCLC, 36 squamous cell carcinomas, 18 adenocarcinomas, stage IIIA/IIIB), apoptotic indices were comparatively analysed before onset and after termination of neoadjuvant therapy. The results were compared with the response to neoadjuvant therapy (extent of therapy-induced tumour regression) as well as the survival times. A statistically significant difference could not be established between pre-therapeutically and post-surgically established apoptotic indices (mean values: 0.93% vs. 1.1%). Neither before therapy nor after surgery did the apoptotic indices show a significant predictive value concerning different overall survival times. These results suggest that neoadjuvant therapy does not modify the extent of apoptosis in lung cancer in the long term. Only a few weeks after the completion of the neoadjuvant chemoradiotherapy this contributes to a net proliferation of the residual tumour tissue which is largely equivalent to that of the untreated tumour.

Adenocarcinoma↗

Esophageal cancer: CT, endoscopic US, and FDG PET for assessment of response to neoadjuvant therapy--systematic review.

PURPOSE: To compare diagnostic accuracy of computed tomography (CT), endoscopic ultrasonography (US), and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for assessment of response to neoadjuvant therapy in patients with esophageal cancer by using a systematic review of the literature. MATERIALS AND METHODS: MEDLINE and EMBASE databases and Cochrane Database of Systematic Reviews were searched for relevant studies. Two reviewers independently assessed the methodological quality of each study. Summary receiver operating characteristic (ROC) analysis was used to summarize and compare the diagnostic accuracy of the three modalities. RESULTS: Four studies with CT, 13 with endoscopic US, and seven with FDG PET met inclusion criteria. Percentages of the maximum score in regard to methodological quality ranged from 15% to 100%. Summary ROC analysis could be performed for three studies with CT, four with endoscopic US, and four with FDG PET. The maximum joint values for sensitivity and specificity were 54% for CT, 86% for endoscopic US, and 85% for FDG PET. Accuracy of CT was significantly lower than that of FDG PET (P < .006) and of endoscopic US (P < .003). Accuracy of FDG PET and that of endoscopic US were similar (P = .839). In all patients, CT was always feasible, whereas endoscopic US was not feasible in 6% of the patients, and FDG PET was not feasible in less than 1%. CONCLUSION: CT has poor accuracy for assessment of response to neoadjuvant therapy in patients with esophageal cancer. Endoscopic US and FDG PET have equivalent good accuracy, but endoscopic US is not always feasible after chemotherapy and radiation therapy. FDG PET seems to be a promising noninvasive tool for assessment of neoadjuvant therapy in patients with esophageal cancer.

Endosonography↗

Preliminary results with neoadjuvant therapy and resection for esophageal carcinoma.

Between December 1988 and August 1992, 68 patients with adenocarcinoma (n = 39) and squamous carcinoma (n = 29) of the esophagus were entered prospectively in a treatment protocol to receive two cycles of cisplatin, 5-fluorouracil, etoposide, leucovorin, and 3,000 cGy of radiation to the involved esophagus and adjacent mediastinum, followed by resection. There were four deaths during chemotherapy, and 7 patients had a decline in condition or were denied operation. Fifty-six patients have come to operation, and 1 awaits resection. Twenty-two patients had transhiatal esophagectomy and 29 patients had esophagogastrostomy with a combined abdominal and right thoracic approach. Five patients did not undergo resection at operation. There was one hospital death (2%). A complete response to preoperative therapy was seen in 12 patients (21%): 5 of 20 with squamous cancer (25%) and 7 of 36 with adenocarcinoma (19%). Average follow-up is 19 months. Median survival in these patients after entrance in the protocol is 24 months. Actuarial survival at 12, 18, and 24 months is 72% (confidence limits, 66% and 78%), 53% (confidence limits, 46% and 60%), and 51% (confidence limits, 44% and 58%). Significantly better survival was associated with adenocarcinoma (p = 0.041). There is no survival advantage based on complete response to preoperative therapy. This neoadjuvant regimen is effective in patients with squamous carcinoma and adenocarcinoma. These preliminary results demonstrate an improved median and actuarial survival compared with historical controls in 137 patients operated on between 1966 and 1985 at our institution.

Adenocarcinoma↗

Remediastinoscopy after neoadjuvant therapy for non-small cell lung cancer.

Despite technical difficulties due to mediastinal fibrosis, remediastinoscopy can be a valuable tool in the restaging of non-small cell lung cancer after neoadjuvant therapy. The aim of our study was to evaluate the feasibility, sensitivity and accuracy of remediastinoscopy. From November 1994 to July 2001 we performed a remediastinoscopy in 27 patients after neoadjuvant therapy. Their age ranged from 35 to 80 years (mean 61.9+/-11.9). In all 27 patients it was possible to perform a remediastinoscopy without major technical difficulties and take biopsies of the lymph nodes that were initially invaded by tumour. Remediastinoscopy was positive in 11 patients (40.7%) and negative in 16 (59.3%). In the 11 patients with a positive remediastinoscopy a complete resection was not judged possible and therefore, an unnecessary thoracotomy was avoided. In four patients, remediastinoscopy turned out to be false negative. So, in our series, sensitivity was 73%, specificity 100% and accuracy 85%. The positive and negative predictive values were 100 and 75%, respectively. Previous mediastinoscopy is no contra-indication for a repeat one after neoadjuvant therapy. Although sensitivity and accuracy are lower than that of a first mediastinoscopy, remediastinoscopy is useful to select patients for surgical resection after induction therapy.

Adult↗

[Complications of extended lung resection procedures following the neoadjuvant therapy].

UNLABELLED: Local tumor expansion in the sense of the tumor invasion into the extrapulmonary structures, which must be removed in one step, preferably en-bloc, together with the primary tumor, is the reason for extending the lung resection procedure. Although verified lymphogenic metastasing into either unilateral, eventually into contralateral mediastinal lymphonodes (stage N2 resp. N3, according to the TNM), remains the commonest indication for the induction therapy in cases of the lung carcinoma, application of the neoadjuvant therapy in cases when extended resections may be expected, is indicated in case the tumor expands into the surrounding structures, which signifies opening of new, unnatural routes of possible lymphogenic and haematogenic dissemination, and thus, a significantly higher risk of the surgical therapy failure. During the period 1995-2002, our team conducted 15 extended lung resection procedures following the preceding induction therapy in patients suffering from the IIB-IIIB stage of the non-small cellular lung carcinoma (NSCLC). The 30-day lethality rate equalled zero. We recorded two rare complications and the postoperative morbidity was acceptable. CONCLUSION: Exhausting staging, the best possible prediction of the tumor behaviour following the surgical procedure and minimal surgical complications remain the prerequisite for good long-term results following the extended lung resections for the lung carcinoma. Application of the neoadjuvant therapy prior to the resection procedure need not increase the risk of surgical complications and, furthermore, may positively affect the disease prognosis.

Carcinoma, Non-Small-Cell Lung↗

Endoscopic ultrasound for esophageal and gastroesophageal junction cancer: Impact of increased use of primary neoadjuvant therapy on preoperative locoregional staging accuracy.

Initial treatment of locally advanced esophageal and gastroesophageal junction (GEJ) malignancies for selected patients at some institutions has recently changed from surgical resection to neoadjuvant therapy. The aim of this study is to evaluate the impact of this change in treatment strategy on both the overall disease profile and locoregional endoscopic ultrasound (EUS) staging accuracy for a cohort of patients managed with primary surgical resection over a 10-year period at our institution. All subjects at our institution who underwent primary esophagectomy from 1993 to 2002 following preoperative EUS for known or suspected esophageal and/or GEJ cancers were identified. Patients with dysplasia alone, prior upper gastrointestinal tract surgery, preoperative neoadjuvant therapy, cancer of the gastric cardia or recurrent malignancy were excluded. EUS findings and staging results were compared to surgical pathology following resection. The impact of the gradually increased use of primary chemoradiation during the second half of the study was assessed. Of the 286 operations performed, 184 subjects were excluded. The remaining 102 underwent primary surgical resection a median of 18 days following EUS staging for adenocarcinoma (88%) or squamous cell carcinoma (12%) of the esophagus (69%) or GEJ (31%). Overall EUS locoregional T and N staging accuracy was 72% and 75% respectively; accuracy for T1, T2, T3 and T4 cancer was 42%, 50%, 88% and 50% respectively. Despite an increased frequency of pathologically confirmed T1 and T2 cancers (P = 0.005) and an insignificant trend toward increased N0 malignancy (P = 0.05) during the second half of the study period, no statistically significant changes in T (P = 0.07) or N (P = 0.82) staging accuracies for EUS or disease characteristics were noted between the first and second half of the study period. Despite both inaccurate radial EUS staging and increased relative use of primary surgery for early cancers, recent increased use of primary neoadjuvant therapy did not change overall disease characteristics and accuracy of locoregional EUS staging of esophageal and GEJ cancers managed with primary surgical resection.

Adenocarcinoma↗

Histologic assessment of non-small cell lung carcinoma after neoadjuvant therapy.

Chemotherapy or chemoradiation is often used in Stage IIIA non-small cell lung carcinoma before surgical resection (neoadjuvant therapy). In reviewing the histopathology of such tumors after resection, the recognition that the pathologic changes are related to prior therapy and the assessment of tumor regression are both of importance. To refine histologic parameters for tumor regression and describe patterns of tumor reaction to therapy, we identified 30 lobectomy or pneumonectomy specimens from 1996-2000 in which neoadjuvant therapy was received before surgical resection. Histologic patterns of treatment-induced tumor regression were analyzed semiquantitatively and included necrosis, fibrosis, mixed inflammatory infiltrate, foamy macrophages, and giant cells. To identify clinical and histologic parameters that correlate with treatment response, the 30 specimens were graded for tumor regression. No correlation was found between tumor regression and age, gender, or type of therapy (chemoradiation versus chemotherapy alone). Squamous cell carcinoma showed a significantly higher rate of response than adenocarcinoma (P =.04), with a significant number of adenocarcinomas in the nonresponder subgroup (P =.05). Tumor size reduction by radiologic assessment, when compared with histologic regression, did not reveal a statistically significant association. However, a positive correlation was found between extent of fibrosis and radiologic estimate of size reduction.

Adenocarcinoma↗

Is there still a role for neoadjuvant therapy in breast cancer?

The role of neoadjuvant chemotherapy in locally advanced breast cancer is firmly established. There is now also an emerging role for neoadjuvant systemic therapy in the treatment of operable breast cancer. There is good evidence that the chances of breast conserving surgery can be increased with this approach and results of randomised studies indicate that survival is at least as good with neoadjuvant as with adjuvant chemotherapy. Similar clinical data are emerging with neoadjuvant endocrine therapy. For the future, there are important potential advantages in having an in vivo measure of chemosensitivity rather than blindly treating micrometastatic disease in the adjuvant setting. Clinical response to neoadjuvant treatment, and in particular complete pathological response, are predictors of subsequent outcome. Pathological involvement of axillary nodes following neoadjuvant therapy portends a poor prognosis. The potential for biological surrogate markers of response to predict for long-term outcome may allow individualisation of systemic treatment and the rapid assessment of new drugs in early breast cancer.

Antineoplastic Agents, Hormonal↗

Integrating clinical and genomic features to predict response to neoadjuvant therapy in microsatellite-stable rectal cancer.

BACKGROUND: Neoadjuvant therapy (NAT) has shifted rectal cancer management toward organ preservation. However, achieving a complete response (CR) for "watch-and-wait" strategies is hindered by high response heterogeneity. Although immunotherapy-combined NAT has expanded the candidate pools, the predictive significance of molecular alterations remains unclear. OBJECTIVES: This study aimed to evaluate clinical and genomic profiles of rectal cancer patients undergoing NAT to identify response predictors and to develop a nomogram for estimating CR probability. DESIGN: Retrospective, single-center cohort study. METHODS: This study included 437 patients with rectal adenocarcinoma at Fudan University Shanghai Cancer Center between December 2019 and March 2023. Patients underwent paired tumor and germline genomic sequencing (887-gene panel) before NAT. Logistic and Cox regression analyses were performed to identify clinical and genetic risk factors associated with tumor response and long-term survival. RESULTS: Of the 437 patients, 96.6% had microsatellite-stable (MSS) tumors. In the MSS locally advanced rectal cancer cohort (N = 307), the CR rate was 35.5%. Multivariate analysis identified immunotherapy-combined NAT (iTNT) (OR 4.41, 95% CI: 2.42-8.27), SYNE1 mutation (OR 2.12, 95% CI: 1.06-4.26), negative mesorectal fascia (MRF) status (OR 0.34, 95% CI: 0.17-0.66), and lower tumor location (OR 0.48, 95% CI: 0.27-0.84) as independent predictors of CR. KRAS mutation was the sole independent predictor of reduced disease-free survival (DFS; HR 1.93, 95% CI: (1.11-3.36), p = 0.020). KRAS G12D subtype was associated with the worst 2-year distant metastasis-free survival (71.3%) and exhibited a distinct predilection for lung metastasis. The clinical-genomic nomogram yielded strong discrimination (AUC = 0.705) and calibration, with favorable DCA net benefit. CONCLUSION: Clinical and genomic features jointly determine outcomes in MSS rectal cancer. SYNE1 mutation serves as a novel biomarker for CR, while KRAS mutations, especially the G12D subtype, identify patients at high risk for systemic relapse. The clinical-genomic nomogram facilitates individualized selection for organ-preservation strategies.

biomarker↗

Sentinel lymph node in esophageal cancer before neoadjuvant therapy.

UNLABELLED: The technique of sentinel lymph node identification and biopsy has become a new popular technique for surgeon to improve staging of malignant diseases. It may also reduce the risk of complication related to standard lymphadenectomy. The method is still in experimental phase in case of esophageal cancer. A possible complication for employment of the method in this tumor is neoadjuvant therapy. The authors developed the technique for identifying and obtaining the sentinel lymph node in esophageal cancer using minimally invasive surgical technique before neoadjuvant therapy. The sentinel lymph node is detected using 99mTc-labelled nanocolloid. The authors report and discuss possible difficulties of the method in the case of a patient with detected sentinel lymph node in this way. CONCLUSION: It is possible to identify and obtain a sentinel lymph node before neoadjuvant therapy in esophageal cancer. On the other hand, the clinical significance and applicability of the method of sentinel lymph node still remains controversial in this kind of a tumor.

Carcinoma, Squamous Cell↗

[Our experience with patients operated after neoadjuvant therapy].

The authors performed thoracotomies on 47 patients because of NSCLC between 1 January 2000 and 31 December 2003. All patients had neoadjuvant therapy which was indicated by IIIA stage NSCLC with N2 nodal status. After the neoadjuvant therapy almost all tumors (92.7%) became resectable. The combinations of therapy types, the operations type and the surgical complications are analysed. Long term outcome proves, that multimodal therapy of NSCLC (in IIIA stage) is an effective treatment method.

Antineoplastic Combined Chemotherapy Protocols↗

Morbidity and mortality after neoadjuvant therapy for lung cancer: the risks of right pneumonectomy.

BACKGROUND: The risks of complications in patients undergoing thoracotomy after neoadjuvant therapy for nonsmall cell lung cancer remain controversial. We reviewed our experience to define it further. METHODS: All patients undergoing thoracotomy after induction chemotherapy from 1993 through 1999 were reviewed. Univariate and multivariate methods for logistic regression model were used to identify predictors of adverse events. RESULTS: Induction chemotherapy included mitomycin, vinblastine, and cisplatin (179 patients), carboplatin and paclitaxel (152 patients), and other combinations (139 patients). Eighty-five patients (18%) received preoperative radiation. Operations were pneumonectomy (97 patients), lobectomy (297 patients), lesser resection (18 patients), and exploration only (58 patients). Total mortality was 7 of 297 (2.4%) and 11 of 97 (11.3%) for all lobectomies and pneumonectomies, respectively, but mortality was 11 of 46 (23.9%) for right pneumonectomy. Complications developed in 179 patients (38%). By multiple regression analysis, right pneumonectomy (p = 0.02), blood loss (p = 0.01), and forced expiratory volume in one second (percent predicted) (p = 0.01) predicted complications. No factor emerged to explain this high right pneumonectomy mortality rate. CONCLUSIONS: Pulmonary resection after neoadjuvant therapy is associated with acceptable overall morbidity and mortality. However, right pneumonectomy is associated with a significantly increased risk and should be performed only in selected patients.

Adult↗