المؤلفون: Mitchell, K G, Nelson, D B, Corsini, E M, Vaporciyan, A A, Antonoff, M B, Mehran, R J, Rice, D C, Roth, J A, Sepesi, B, Walsh, G L, Bhutani, M S, Maru, D M, Wu, C C, Nguyen, Q-N, Ajani, J A, Swisher, S G, Hofstetter, W L

المصدر: Diseases of the Esophagus ; ISSN 1120-8694 1442-2050

مصطلحات موضوعية: Gastroenterology, General Medicine

الوصف: SUMMARY The survival advantage associated with the addition of surgical therapy in esophageal squamous cell carcinoma (ESCC) patients who demonstrate a complete clinical response to chemoradiotherapy is unclear, and many institutions have adopted an organ-preserving strategy of selective surgery in this population. We sought to characterize our institutional experience of salvage esophagectomy (for failure of definitive bimodality therapy) and planned esophagectomy (as a component of trimodality therapy) by retrospectively analyzing patients with ESCC of the thoracic esophagus and GEJ who underwent esophagectomy following chemoradiotherapy between 2004 and 2016. Of 76 patients who met inclusion criteria, 46.1% (35) underwent salvage esophagectomy. Major postoperative complications (major cardiovascular and pulmonary events, anastomotic leak [grade ≥ 2], and 90-day mortality) were frequent and occurred in 52.6% of the cohort (planned resection: 36.6% [15/41]; salvage esophagectomy: 71.4% [25/35]). Observed rates of 30- and 90-day mortality for the entire cohort were 7.9% (planned: 7.3% [3/41]; salvage: 8.6% [3/35]) and 13.2% (planned: 9.8% [4/41]; salvage: 17.1% [6/35]), respectively. In summary, esophagectomy following chemoradiotherapy for ESCC at our institution has been associated with frequent postoperative morbidity and considerable rates of mortality in both planned and salvage settings. Although a selective approach to surgery may permit organ preservation in many patients with ESCC, these results highlight that salvage esophagectomy for failure of definitive-intent treatment of ESCC may also constitute a difficult clinical undertaking in some cases.

الإتاحة: https://doi.org/10.1093/dote/doz067Test

المؤلفون: Gay C. M., Stewart C. A., Park E. M., Diao L., Groves S. M., Heeke S., Nabet B. Y., Fujimoto J., Solis L. M., Lu W., Xi Y., Cardnell R. J., Wang Q., Fabbri G., Cargill K. R., Vokes N. I., Ramkumar K., Zhang B., Della Corte C. M., Robson P., Swisher S. G., Roth J. A., Glisson B. S., Shames D. S., Wistuba I. I., Wang J., Quaranta V., Minna J., Heymach J. V., Byers L. A.

المساهمون: Gay, C. M., Stewart, C. A., Park, E. M., Diao, L., Groves, S. M., Heeke, S., Nabet, B. Y., Fujimoto, J., Solis, L. M., Lu, W., Xi, Y., Cardnell, R. J., Wang, Q., Fabbri, G., Cargill, K. R., Vokes, N. I., Ramkumar, K., Zhang, B., Della Corte, C. M., Robson, P., Swisher, S. G., Roth, J. A., Glisson, B. S., Shames, D. S., Wistuba, I. I., Wang, J., Quaranta, V., Minna, J., Heymach, J. V., Byers, L. A.

مصطلحات موضوعية: ASCL1, EMT, intratumoral heterogeneity, NEUROD1, neuroendocrine, POU2F3, SCLC, Animal, Cell Line, Tumor, Cisplatin, Female, Gene Expression Regulation, Neoplastic, Human, Immunity, Lung Neoplasm, Mice, Nude, Prognosi, Small Cell Lung Carcinoma, Transcription Factors

الوصف: Despite molecular and clinical heterogeneity, small cell lung cancer (SCLC) is treated as a single entity with predictably poor results. Using tumor expression data and non-negative matrix factorization, we identify four SCLC subtypes defined largely by differential expression of transcription factors ASCL1, NEUROD1, and POU2F3 or low expression of all three transcription factor signatures accompanied by an Inflamed gene signature (SCLC-A, N, P, and I, respectively). SCLC-I experiences the greatest benefit from the addition of immunotherapy to chemotherapy, while the other subtypes each have distinct vulnerabilities, including to inhibitors of PARP, Aurora kinases, or BCL-2. Cisplatin treatment of SCLC-A patient-derived xenografts induces intratumoral shifts toward SCLC-I, supporting subtype switching as a mechanism of acquired platinum resistance. We propose that matching baseline tumor subtype to therapy, as well as manipulating subtype switching on therapy, may enhance depth and duration of response for SCLC patients. Gay et al. provide a classification for four subtypes of small cell lung cancer, each with unique molecular features and therapeutic vulnerabilities. An inflamed, mesenchymal subtype predicts benefit with the addition of immunotherapy to chemotherapy. Intratumoral switching between chemosensitive and chemoresistant subtypes accompanies therapeutic resistance.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33482121; info:eu-repo/semantics/altIdentifier/wos/WOS:000627120300010; volume:39; issue:3; firstpage:346; lastpage:360.e7; journal:CANCER CELL; http://hdl.handle.net/11591/462644Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85100528860

الإتاحة: https://doi.org/10.1016/j.ccell.2020.12.014Test
http://hdl.handle.net/11591/462644Test

المؤلفون: Zhou, N, Mitchell, K G, Corsini, E M, Truong, V T T, Antonoff, M B, Mehran, R J, Rajaram, R, Rice, D C, Roth, J A, Sepesi, B, Swisher, S G, Vaporciyan, A A, Walsh, G L, Ajani, J A, Hofstetter, W L

المساهمون: Mason Family Research Fund

المصدر: British Journal of Surgery ; volume 108, issue 10, page 1207-1215 ; ISSN 0007-1323 1365-2168

مصطلحات موضوعية: Surgery

الوصف: Background Long-term survival outcomes of trimodal therapy (TMT; chemoradiation plus surgery) and bimodal therapy (BMT; chemoradiation) have seldom been analysed. In a selective-surgery paradigm, the benefit of TMT in patients with a complete clinical response is controversial. Factors associated with survival in patients with a clinical complete response to chemoradiation were evaluated. Methods Patients with stage II–III oesophageal squamous cell carcinoma treated with TMT or BMT from 2002 to 2017 were evaluated. The BMT group consisted of patients who were otherwise eligible for surgery but underwent chemoradiation alone followed by observation. This group included patients who later had salvage oesophagectomy. Survival was evaluated and compared between TMT and BMT groups. Elastic net regularization was performed to select co-variables for Cox multivariable survival analysis in patients with a clinical complete response. Results Of 143 patients, 60 (41.9 per cent) underwent TMT and 83 (58.0 per cent) BMT. Patients who underwent TMT had longer median overall survival than those who had BMT (77 versus 33 months; P = 0.019). For patients with a clinical complete response, TMT achieved longer median overall survival than BMT (123 versus 55 months; P = 0.04). BMT had a high locoregional recurrence rate (48 versus 6 per cent; P < 0.001); 26 of 29 patients with locoregional recurrence in the BMT groupunderwent salvage resection. Cox multivariable analysis demonstrated that upper–mid oesophageal tumour location (hazard ratio (HR) 2.04; P = 0.024) and tumour length (HR 1.18; P = 0.046) were associated with worse survival. Although TMT was not associated with survival, it was a predictor of reduced recurrence (HR 0.28; P = 0.028). The maximum standardized uptake value after chemoradiation also predicted recurrence (HR 1.33; P < 0.001). Conclusion In patients who achieve a clinical complete response, TMT reduces locoregional recurrence but may not prolong survival. The differences in survival ...

الإتاحة: https://doi.org/10.1093/bjs/znab162Test
https://academic.oup.com/bjs/article-pdf/108/10/1207/50744837/znab162.pdfTest

المؤلفون: Travis W. D., Dacic S., Wistuba I., Sholl L., Adusumilli P., Bubendorf L., Bunn P., Cascone T., Chaft J., Chen G., Chou T. -Y., Cooper W., Erasmus J. J., Ferreira C. G., Goo J. -M., Heymach J., Hirsch F. R., Horinouchi H., Kerr K., Kris M., Jain D., Kim Y. T., Lopez-Rios F., Lu S., Mitsudomi T., Moreira A., Motoi N., Nicholson A. G., Oliveira R., Papotti M., Pastorino U., Paz-Ares L., Pelosi G., Poleri C., Provencio M., Roden A. C., Scagliotti G., Swisher S. G., Thunnissen E., Tsao M. S., Vansteenkiste J., Weder W., Yatabe Y.

المساهمون: Travis W.D., Dacic S., Wistuba I., Sholl L., Adusumilli P., Bubendorf L., Bunn P., Cascone T., Chaft J., Chen G., Chou T.-Y., Cooper W., Erasmus J.J., Ferreira C.G., Goo J.-M., Heymach J., Hirsch F.R., Horinouchi H., Kerr K., Kris M., Jain D., Kim Y.T., Lopez-Rios F., Lu S., Mitsudomi T., Moreira A., Motoi N., Nicholson A.G., Oliveira R., Papotti M., Pastorino U., Paz-Ares L., Pelosi G., Poleri C., Provencio M., Roden A.C., Scagliotti G., Swisher S.G., Thunnissen E., Tsao M.S., Vansteenkiste J., Weder W., Yatabe Y.

مصطلحات موضوعية: Lung Cancer, Neoadjuvant therapy, Pathology, Resection specimen, Specimen processing, Treatment response, Human, Lung, Lung Neoplasm

الوصف: Currently, there is no established guidance on how to process and evaluate resected lung cancer specimens after neoadjuvant therapy in the setting of clinical trials and clinical practice. There is also a lack of precise definitions on the degree of pathologic response, including major pathologic response or complete pathologic response. For other cancers such as osteosarcoma and colorectal, breast, and esophageal carcinomas, there have been multiple studies investigating pathologic assessment of the effects of neoadjuvant therapy, including some detailed recommendations on how to handle these specimens. A comprehensive mapping approach to gross and histologic processing of osteosarcomas after induction therapy has been used for over 40 years. The purpose of this article is to outline detailed recommendations on how to process lung cancer resection specimens and to define pathologic response, including major pathologic response or complete pathologic response after neoadjuvant therapy. A standardized approach is recommended to assess the percentages of (1) viable tumor, (2) necrosis, and (3) stroma (including inflammation and fibrosis) with a total adding up to 100%. This is recommended for all systemic therapies, including chemotherapy, chemoradiation, molecular-targeted therapy, immunotherapy, or any future novel therapies yet to be discovered, whether administered alone or in combination. Specific issues may differ for certain therapies such as immunotherapy, but the grossing process should be similar, and the histologic evaluation should contain these basic elements. Standard pathologic response assessment should allow for comparisons between different therapies and correlations with disease-free survival and overall survival in ongoing and future trials. The International Association for the Study of Lung Cancer has an effort to collect such data from existing and future clinical trials. These recommendations are intended as guidance for clinical trials, although it is hoped they can be viewed as suggestion ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/32004713; info:eu-repo/semantics/altIdentifier/wos/WOS:000531550600009; volume:15; issue:5; firstpage:709; lastpage:740; numberofpages:32; journal:JOURNAL OF THORACIC ONCOLOGY; http://hdl.handle.net/2318/1785582Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85081912352

الإتاحة: https://doi.org/10.1016/j.jtho.2020.01.005Test
http://hdl.handle.net/2318/1785582Test

المؤلفون: Ajani, J. A., Xiao, L., Roth, J. A., Hofstetter, W. L., Walsh, G., Komaki, R., Liao, Z., Rice, D. C., Vaporciyan, A. A., Maru, D. M., Lee, J. H., Bhutani, M. S., Eid, A., Yao, J. C., Phan, A. P., Halpin, A., Suzuki, A., Taketa, T., Thall, P. F., Swisher, S. G.

مصطلحات موضوعية: Original article

الوصف: Background The contribution of induction chemotherapy (IC) before preoperative chemoradiation for esophageal cancer (EC) is not known. We hypothesized that IC would increase the rate of pathologic complete response (pathCR). Methods Trimodality-eligibile patients were randomized to receive no IC (Arm A) or IC (oxaliplatin/FU; Arm B) before oxaliplatin/FU/radiation. Surgery was attempted ∼5–6 weeks after chemoradiation. The pathCR rate, post-surgery 30-day mortality, overall survival (OS), and toxic effects were assessed. Bayesian methods and Fisher's exact test were used. Results One hundred twenty-six patients were randomized dynamically to balance the two arms for histology, baseline stage, gender, race, and age. Fifty-five patients in Arm A and 54 in Arm B underwent surgery. The median actuarial OS for all patients (54 deaths) was 45.62 months [95% confidence interval (CI), 27.63–NA], with median OS 45.62 months (95% CI 25.56–NA) in Arm A and 43.68 months (95% CI 27.63–NA) in Arm B ( P = 0.69). The pathCR rate in Arm A was 13% (7 of 55) and 26% (14 of 54) in Arm B (two-sided Fisher's exact test, P = 0.094). Safety was similar in both arms. Conclusions These data suggest that IC produces non-significant increase in the pathCR rate and does not prolong OS. Further development of IC before chemoradiation may not be beneficial. Clinical trial no.: NCT 00525915 ( www.clinicaltrials.gov ).

وصف الملف: text/html

العلاقة: http://annonc.oxfordjournals.org/cgi/content/short/mdt339v1Test; http://dx.doi.org/10.1093/annonc/mdt339Test

الإتاحة: https://doi.org/10.1093/annonc/mdt339Test
http://annonc.oxfordjournals.org/cgi/content/short/mdt339v1Test

المؤلفون: Suzuki, A., Xiao, L., Taketa, T., Sudo, K., Wadhwa, R., Blum, M. A., Skinner, H., Komaki, R., Weston, B., Lee, J. H., Bhutani, M. S., Rice, D. C., Maru, D. M., Erasmus, J., Swisher, S. G., Hofstetter, W. L., Ajani, J. A.

مصطلحات موضوعية: Original article

الوصف: Background Patients with localized esophageal adenocarcinoma (EAC) who achieve a clinical complete response (clinCR) after preoperative chemoradiation (trimodality therapy; TMT) or definitive chemoradiation (bimodality therapy; BMT) live longer than those who achieve a

وصف الملف: text/html

العلاقة: http://annonc.oxfordjournals.org/cgi/content/short/mdt340v1Test; http://dx.doi.org/10.1093/annonc/mdt340Test

الإتاحة: https://doi.org/10.1093/annonc/mdt340Test
http://annonc.oxfordjournals.org/cgi/content/short/mdt340v1Test

المؤلفون: Cheedella, N. K. S., Suzuki, A., Xiao, L., Hofstetter, W. L., Maru, D. M., Taketa, T., Sudo, K., Blum, M. A., Lin, S. H., Welch, J., Lee, J. H., Bhutani, M. S., Rice, D. C., Vaporciyan, A. A., Swisher, S. G., Ajani, J. A.

مصطلحات موضوعية: gastrointestinal tumors

الوصف: Background Chemoradiation followed by surgery is the preferred treatment of localized gastroesophageal cancer (GEC). Surgery causes considerable life-altering consequences and achievement of clinical complete response (clinCR; defined as postchemoradiation [but presurgery] endoscopic biopsy negative for cancer and positron emission tomographic (PET) scan showing physiologic uptake) is an enticement to avoid/delay surgery. We examined the association between clinCR and pathologic complete response (pathCR). Patients and methods Two hundred eighty-four patients with GEC underwent chemoradiation and esophagectomy. The chi-square test, Fisher exact test, t -test, Kaplan–Meier method, and log-rank test were used. Results Of 284 patients, 218 (77%) achieved clinCR. However, only 67 (31%) of the 218 achieved pathCR. The sensitivity of clinCR for pathCR was 97.1% (67/69), but the specificity was low (29.8%; 64/215). Of the 66 patients who had less than a clinCR, only 2 (3%) had a pathCR. Thus, the rate of pathCR was significantly different in patients with clinCR than in those with less than a clinCR ( P < 0.001). Conclusions clinCR is not highly associated with pathCR; the specificity of clinCR for pathCR is too low to be used for clinical decision making on delaying/avoiding surgery. Surgery-eligible GEC patients should be encouraged to undergo surgery following chemoradiation despite achieving a clinCR.

وصف الملف: text/html

العلاقة: http://annonc.oxfordjournals.org/cgi/content/short/24/5/1262Test; http://dx.doi.org/10.1093/annonc/mds617Test

الإتاحة: https://doi.org/10.1093/annonc/mds617Test
http://annonc.oxfordjournals.org/cgi/content/short/24/5/1262Test

المؤلفون: Lopez Guerra, J. L., Gomez, D. R., Lin, S. H., Levy, L. B., Zhuang, Y., Komaki, R., Jaen, J., Vaporciyan, A. A., Swisher, S. G., Cox, J. D., Liao, Z., Rice, D. C.

مصطلحات موضوعية: lung cancer

الوصف: Background The purpose of this study was to evaluate the actuarial risk of local and regional failure in patients with completely resected non-small-cell lung cancer (NSCLC), and to assess surgical and pathological factors affecting this risk. Patients and methods Between January 1998 and December 2009, 1402 consecutive stage I–III (N0–N1) NSCLC patients underwent complete resection without adjuvant radiation therapy. The median follow-up was 42 months. Results Local–regional recurrence was identified in 9% of patients, with local failure alone in 3% of patients, regional failure alone in 4% of patients, and both local and regional failure simultaneously in 2% of patients. Patients who had local failure were found to be at increased risk of mortality. By multivariate analyses, three variables were shown to be independently significant risk factors for local [surgical procedure (single/multiple wedges + segmentectomy versus lobectomy + bilobectomy + pneumonectomy), tumor size >2.7 cm, and visceral pleural invasion] and regional (pathologic N1 stage, visceral pleural invasion, and lymphovascular space invasion, LVI) recurrence, respectively. Conclusion Patients with N0–N1 disease have low rates of locoregional recurrence after surgical resection. However, several prognostic factors can be identified that increase this risk and identify patients who may benefit from adjuvant treatment.

وصف الملف: text/html

العلاقة: http://annonc.oxfordjournals.org/cgi/content/short/24/1/67Test; http://dx.doi.org/10.1093/annonc/mds274Test

الإتاحة: https://doi.org/10.1093/annonc/mds274Test
http://annonc.oxfordjournals.org/cgi/content/short/24/1/67Test

المؤلفون: Cheedella, N. K. S., Suzuki, A., Xiao, L., Hofstetter, W. L., Maru, D. M., Taketa, T., Sudo, K., Blum, M. A., Lin, S. H., Welch, J., Lee, J. H., Bhutani, M. S., Rice, D. C., Vaporciyan, A. A., Swisher, S. G., Ajani, J. A.

مصطلحات موضوعية: Original article

الوصف: Background Chemoradiation followed by surgery is the preferred treatment of localized gastroesophageal cancer (GEC). Surgery causes considerable life-altering consequences and achievement of clinical complete response (clinCR; defined as postchemoradiation [but presurgery] endoscopic biopsy negative for cancer and positron emission tomographic (PET) scan showing physiologic uptake) is an enticement to avoid/delay surgery. We examined the association between clinCR and pathologic complete response (pathCR). Patients and methods Two hundred eighty-four patients with GEC underwent chemoradiation and esophagectomy. The chi-square test, Fisher exact test, t -test, Kaplan–Meier method, and log-rank test were used. Results Of 284 patients, 218 (77%) achieved clinCR. However, only 67 (31%) of the 218 achieved pathCR. The sensitivity of clinCR for pathCR was 97.1% (67/69), but the specificity was low (29.8%; 64/215). Of the 66 patients who had less than a clinCR, only 2 (3%) had a pathCR. Thus, the rate of pathCR was significantly different in patients with clinCR than in those with less than a clinCR ( P < 0.001). Conclusions clinCR is not highly associated with pathCR; the specificity of clinCR for pathCR is too low to be used for clinical decision making on delaying/avoiding surgery. Surgery-eligible GEC patients should be encouraged to undergo surgery following chemoradiation despite achieving a clinCR.

وصف الملف: text/html

العلاقة: http://annonc.oxfordjournals.org/cgi/content/short/mds617v1Test; http://dx.doi.org/10.1093/annonc/mds617Test

الإتاحة: https://doi.org/10.1093/annonc/mds617Test
http://annonc.oxfordjournals.org/cgi/content/short/mds617v1Test

المؤلفون: Lopez Guerra, J. L., Gomez, D. R., Lin, S. H., Levy, L. B., Zhuang, Y., Komaki, R., Jaen, J., Vaporciyan, A. A., Swisher, S. G., Cox, J. D., Liao, Z., Rice, D. C.

مصطلحات موضوعية: Original article

الوصف: Background The purpose of this study was to evaluate the actuarial risk of local and regional failure in patients with completely resected non-small-cell lung cancer (NSCLC), and to assess surgical and pathological factors affecting this risk. Patients and methods Between January 1998 and December 2009, 1402 consecutive stage I–III (N0–N1) NSCLC patients underwent complete resection without adjuvant radiation therapy. The median follow-up was 42 months. Results Local–regional recurrence was identified in 9% of patients, with local failure alone in 3% of patients, regional failure alone in 4% of patients, and both local and regional failure simultaneously in 2% of patients. Patients who had local failure were found to be at increased risk of mortality. By multivariate analyses, three variables were shown to be independently significant risk factors for local [surgical procedure (single/multiple wedges + segmentectomy versus lobectomy + bilobectomy + pneumonectomy), tumor size >2.7 cm, and visceral pleural invasion] and regional (pathologic N1 stage, visceral pleural invasion, and lymphovascular space invasion, LVI) recurrence, respectively. Conclusion Patients with N0–N1 disease have low rates of locoregional recurrence after surgical resection. However, several prognostic factors can be identified that increase this risk and identify patients who may benefit from adjuvant treatment.

وصف الملف: text/html

العلاقة: http://annonc.oxfordjournals.org/cgi/content/short/mds274v1Test; http://dx.doi.org/10.1093/annonc/mds274Test

الإتاحة: https://doi.org/10.1093/annonc/mds274Test
http://annonc.oxfordjournals.org/cgi/content/short/mds274v1Test