Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint

Hellmann, Matthew D; Chaft, Jamie E; William, William N; Rusch, Valerie; Pisters, Katherine M W; Kalhor, Neda; Pataer, Apar; Travis, William D; Swisher, Stephen G; Kris, Mark G

doi:10.1016/s1470-2045(13)70334-6

Cited by 646Lung Cancer Diagnosis and TreatmentLung Cancer Treatments and MutationsLung Cancer Research Studies

Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint

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Hellmann, Matthew D, Chaft, Jamie E, William, William N, Rusch, Valerie, Pisters, Katherine M W, Kalhor, Neda, Pataer, Apar, Travis, William D +2 more·2014·The Lancet Oncology

DOI 10.1016/s1470-2045(13)70334-6PMC PMC4734624

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Abstract

Improvements in outcomes for patients with resectable lung cancers have plateaued. Clinical trials of resectable non-small-cell lung cancers with overall survival as the primary endpoint require a decade or longer to complete, are expensive, and limit innovation. A surrogate for survival, such as pathological response to neoadjuvant chemotherapy, has the potential to improve the efficiency of trials and expedite advances. 10% or less residual viable tumour after neoadjuvant chemotherapy, termed here major pathological response, meets criteria for a surrogate; major pathological response strongly associates with improved survival, is reflective of treatment effect, and captures the magnitude of the treatment benefit on survival. We support the incorporation of major pathological response as a surrogate endpoint for survival in future neoadjuvant trials of resectable lung cancers. Additional prospective studies are needed to confirm the validity and reproducibility of major pathological response within individual histological and molecular subgroups and with new drugs.

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In other cancer types, the endpoint to define response to neoadjuvant therapy has been pathological complete response (100%) or near-pathological complete response (>90%).
“In other cancer types, the endpoint to define response to neoadjuvant therapy has been pathological complete response (100%)13,15 or near-pathological complete response (>90%).29”
From Pathological response following neoadjuvant immune checkpoint inhibitors in patients with hepatocellular carcinoma: a cross-trial, patient-level analysis (2024) · cites this paper as [29]
Section 2 (page unavailable) proposes major pathological response as ≤10% residual tumor tissue—approximately >90% response—as an endpoint after neoadjuvant chemotherapy. But that proposal concerns resectable non-small-cell lung cancer, not the use of near-complete response as an endpoint in other cancer types. Section 5 discusses pathological complete response as an endpoint in breast cancer, without establishing the cited >90% threshold there. (LLM, conf=0.83)
Experimental — accuracy not yet measured
A positive association exists between MPR to neoadjuvant chemotherapy and improved survival in operable NSCLC.
“The realization that a positive association exists between an MPR (≤10% viable tumor in resected tumor specimens) to neoadjuvant chemotherapy and improved survival outcomes in patients with operable NSCLC4–7”
From Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial (2021) · cites this paper as [5]
Several clinical trials of neoadjuvant platinum doublet chemotherapy have reported a median pCR rate of only 4%.
“In comparison, several clinical trials of neoadjuvant platinum doublet chemotherapy have reported a median pCR rate of only of 4%5,”
From Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial (2021) · cites this paper as [5]

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Definition and Impact of Pathologic Complete Response on Prognosis After Neoadjuvant Chemotherapy in Various Intrinsic Breast Cancer Subtypes
von Minckwitz, G., Untch, M., Blohmer, J.-U., Costa, S. D., Eidtmann, H., Fasching, P. A., Gerber, B., Eiermann, W., Hilfrich, J., Huober, J., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.38.8595 · Cited by 2,659 · see citing works
Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group.
Pignon, J.-P., Tribodet, H., Scagliotti, G. V., Douillard, J.-Y., Shepherd, F. A., Stephens, R. J., Dunant, A., Torri, V., Rosell, R., Seymour, L., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.9030 · Cited by 2,642 · see citing works
Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial
Gianni, L., Pieńkowski, T., Im, Y., Roman, L., Tseng, L., Liu, M.-C., Lluch, A. M., Starosławska, E., de la Haba-Rodríguez, J., Im, S., et al. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70336-9 · Cited by 2,393 · see citing works
Cisplatin-Based Adjuvant Chemotherapy in Patients with Completely Resected Non–Small-Cell Lung Cancer
The International Adjuvant Lung Cancer Trial Collaborative Group (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031644 · Cited by 2,334 · see citing works
Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.
Fisher, B., Bryant, J., Wolmark, N., Mamounas, E. P., Brown, A., Fisher, E. R., Wickerham, D. L., Begovič, M., DeCillis, A. P., Robidoux, A., et al. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.8.2672 · Cited by 2,164 · see citing works
Surrogate endpoints in clinical trials: Definition and operational criteria
Prentice, R. L. (1989) · Statistics in Medicine · doi:10.1002/sim.4780080407 · Cited by 2,057 · see citing works
Vinorelbine plus Cisplatin vs. Observation in Resected Non–Small-Cell Lung Cancer
Winton, T. L., Livingston, R. B., Johnson, D. H., Rigas, J. R., Johnston, M., Butts, C. A., Cormier, Y. F., Goss, G., Inculet, R., Vallières, E., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043623 · Cited by 1,810 · see citing works
Preoperative Chemotherapy: Updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27
Rastogi, P., Anderson, S. J., Bear, H. D., Geyer, C. E., Kahlenberg, M. S., Robidoux, A., Margolese, R. G., Hoehn, J. L., Vogel, V. G., Dakhil, S. R., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.0235 · Cited by 1,789 · see citing works
Surrogate End Points in Clinical Trials: Are We Being Misled?
Fleming, T. R., & DeMets, D. L. (1996) · Annals of Internal Medicine · doi:10.7326/0003-4819-125-7-199610010-00011 · Cited by 1,651 · see citing works
Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB–IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial
Douillard, J., Rosell, R., Lena, M. D., Carpagnano, F., Ramlau, R., González-Larriba, J. L., Grodzki, T., Pereira, J. R., Groumellec, A. L., Lorusso, V., et al. (2006) · The Lancet Oncology · doi:10.1016/s1470-2045(06)70804-x · Cited by 1,573 · see citing works
Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial
Albain, K. S., Swann, R. S., Rusch, V. W., Turrisi, A. T., Shepherd, F. A., Smith, C. J., Chen, Y., Livingston, R. B., Feins, R. H., Gandara, D. R., et al. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60737-6 · Cited by 1,472 · see citing works
Self-citation
Clinical Course of Breast Cancer Patients With Complete Pathologic Primary Tumor and Axillary Lymph Node Response to Doxorubicin-Based Neoadjuvant Chemotherapy
Kuerer, H. M., Newman, L. A., Smith, T. L., Ames, F. C., Hunt, K. K., Dhingra, K., Theriault, R. L., Singh, G., Binkley, S. M., Sneige, N., et al. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.2.460 · Cited by 1,329 · see citing works
Preoperative Chemotherapy in Patients With Operable Breast Cancer: Nine-Year Results From National Surgical Adjuvant Breast and Bowel Project B-18
Wolmark, N., Wang, J., Mamounas, E., Bryant, J., & Fisher, B. (2001) · JNCI Monographs · doi:10.1093/oxfordjournals.jncimonographs.a003469 · Cited by 1,299 · see citing works
A Randomized Trial Comparing Preoperative Chemotherapy Plus Surgery with Surgery Alone in Patients with Non-Small-Cell Lung Cancer
Rosell, R., Gómez‐Codina, J., Camps, C., Maestre, J., Padille, J., Cantó, A., Mate, J. L., Li, S., Roig, J., Zudaire, Á. O., et al. (1994) · New England Journal of Medicine · doi:10.1056/nejm199401203300301 · Cited by 1,257 · see citing works
Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort
Gianni, L., Eiermann, W., Semiglazov, V., Manikhas, A., Lluch, A., Tjulandin, S., Zambetti, M., Vazquez, F., Byakhow, M., Lichinitser, M., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61964-4 · Cited by 1,255 · see citing works
Significantly Higher Pathologic Complete Remission Rate After Neoadjuvant Therapy With Trastuzumab, Paclitaxel, and Epirubicin Chemotherapy: Results of a Randomized Trial in Human Epidermal Growth Factor Receptor 2–Positive Operable Breast Cancer
Buzdar, A. U., Ibrahim, N. K., Francis, D., Booser, D. J., Thomas, E. S., Theriault, R. L., Pusztai, L., Green, M. C., Arun, B., Giordano, S. H., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.07.032 · Cited by 1,170 · see citing works
The Effect on Tumor Response of Adding Sequential Preoperative Docetaxel to Preoperative Doxorubicin and Cyclophosphamide: Preliminary Results From National Surgical Adjuvant Breast and Bowel Project Protocol B-27
Bear, H. D., Anderson, S., Brown, A. M., Smith, R. E., Mamounas, E. P., Fisher, B., Margolese, R. G., Theoret, H., Soran, A., Wickerham, D. L., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.12.005 · Cited by 1,118 · see citing works
A Randomized Trial Comparing Perioperative Chemotherapy and Surgery With Surgery Alone in Resectable Stage IIIA Non-Small-Cell Lung Cancer
Roth, J. A., Fossella, F. V., Komaki, R., Ryan, M., Putnam, J. B., Lee, J. S., Dhingra, H. M., Caro, L. D., Chasen, M. R., McGavran, M. H., et al. (1994) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/86.9.673 · Cited by 1,107 · see citing works
Preoperative Chemotherapy in Primary Operable Breast Cancer: Results From the European Organization for Research and Treatment of Cancer Trial 10902
van der Hage, J. A., van de Velde, C. J. �., Julien, J.-P., Tubiana-Hulin, M., Vandervelden, C., Duchateau, L., & Cooperating Investigators (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.22.4224 · Cited by 1,105 · see citing works
Preoperative chemotherapy for osteogenic sarcoma:Selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy
Rosen, G., Caparros, B., Huvos, A. G., Kosloff, C., Nirenberg, A., Cacavio, A., Marcove, R. C., Lane, J. M., Mehta, B. M., & Urban, C. (1982) · Cancer · doi:10.1002/1097-0142(19820315)49:6 · Cited by 1,088 · see citing works
Adjuvant Paclitaxel Plus Carboplatin Compared With Observation in Stage IB Non–Small-Cell Lung Cancer: CALGB 9633 With the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups
Strauss, G. M., Herndon, J. E., Maddaus, M. A., Johnstone, D. W., Johnson, E. A., Harpole, D. H., Gillenwater, H. H., Watson, D. M., Sugarbaker, D. J., Schilsky, R. L., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.4855 · Cited by 973 · see citing works
Sequential Preoperative or Postoperative Docetaxel Added to Preoperative Doxorubicin Plus Cyclophosphamide for Operable Breast Cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27
Bear, H. D., Anderson, S., Smith, R. E., Geyer, C. E., Mamounas, E. P., Fisher, B., Brown, A. M., Robidoux, A., Margolese, R. G., Kahlenberg, M. S., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.1665 · Cited by 943 · see citing works
Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805.
Albain, K. S., Rusch, V. W., Crowley, J. J., Rice, T. W., Turrisi, A. T., Weick, J. K., Lonchyna, V. A., Presant, C. A., McKenna, R., & Gandara, D. R. (1995) · Journal of Clinical Oncology · doi:10.1200/jco.1995.13.8.1880 · Cited by 855 · see citing works
Self-citation
Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer
Haller, D. G., Tabernero, J. M., Maroun, J. A., de Braud, F., Price, T. J., Cutsem, E. V., Hill, M. E., Gilberg, F., Rittweger, K., & Schmoll, H. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.6297 · Cited by 782 · see citing works
Disease-free survival versus overall survival as a primary end point for adjuvant colon cancer studies: individual patient data from 20,898 patients on 18 randomized trials
Sargent, D. J., Wieand, H. S., Haller, D. G., Gray, R., Benedetti, J. K., Buyse, M., Labianca, R., Seitz, J. F., O'Callaghan, C. J., Francini, G., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.01.6071 · Cited by 713 · see citing works
Randomized Controlled Trial of Resection Versus Radiotherapy After Induction Chemotherapy in Stage IIIA-N2 Non-Small-Cell Lung Cancer
van Meerbeeck, J. P., Kramer, G. W. P. M., Schil, P. E. V., et al. (2007) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djk093 · Cited by 706 · see citing works
Review of the Comparative Pharmacology and Clinical Activity of Cisplatin and Carboplatin
Go, R. S., & Adjei, A. A. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.1.409 · Cited by 698 · see citing works
Preoperative Chemotherapy Followed by Surgery Compared With Primary Surgery in Resectable Stage I (Except T1N0), II, and IIIa Non-Small-Cell Lung Cancer
Depierre, A., Milleron, B. J., Moro‐Sibilot, D., Chevret, S., Quoix, É., Lebeau, B., Braun, D., Breton, J.-L., Lemarié, É., Gouva, S., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.20.1.247 · Cited by 647 · see citing works
Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data
Arriagada, R. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60059-1 · Cited by 636 · see citing works
Prognostic Value of Pathologic Complete Response After Primary Chemotherapy in Relation to Hormone Receptor Status and Other Factors
Guarneri, V., Broglio, K. R., Kau, S., Cristofanilli, M., Buzdar, A. U., Valero, V., Buchholz, T. A., Meric, F., Middleton, L. P., Hortobágyi, G. N., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.6914 · Cited by 600 · see citing works
Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy
Houssami, N., Macaskill, P., von Minckwitz, G., Marinovich, M. L., & Mamounas, E. P. (2012) · European Journal of Cancer · doi:10.1016/j.ejca.2012.05.023 · Cited by 554 · see citing works
Neoadjuvant Chemotherapy and Bevacizumab for HER2-Negative Breast Cancer
von Minckwitz, G., Eidtmann, H., Rezai, M., Fasching, P. A., Tesch, H., Eggemann, H., Schrader, I., Kittel, K., Hanusch, C. A., Kreienberg, R., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1111065 · Cited by 529 · see citing works
Pathologic Complete Response After Neoadjuvant Chemotherapy Plus Trastuzumab Predicts Favorable Survival in Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer: Results From the TECHNO Trial of the AGO and GBG Study Groups
Untch, M., Fasching, P. A., Konecny, G. E., Hasmüller, S., Lebeau, A., Kreienberg, R., Camara, O., Müller, V., du Bois, A., Kühn, T., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.31.4930 · Cited by 502 · see citing works
Effect of Oxaliplatin, Fluorouracil, and Leucovorin With or Without Cetuximab on Survival Among Patients With Resected Stage III Colon Cancer
Sargent, D. J. (2012) · JAMA · doi:10.1001/jama.2012.385 · Cited by 497 · see citing works
End Points and United States Food and Drug Administration Approval of Oncology Drugs
Johnson, J. R., Williams, G., & Pazdur, R. M. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.08.072 · Cited by 480 · see citing works
Neoadjuvant Therapy with Paclitaxel followed by 5-Fluorouracil, Epirubicin, and Cyclophosphamide Chemotherapy and Concurrent Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Operable Breast Cancer: An Update of the Initial Randomized Study Population and Data of Additional Patients Treated with the Same Regimen
Buzdar, A. U., Valero, V., Ibrahim, N. K., Francis, D., Broglio, K. R., Theriault, R. L., Pusztai, L., Green, M. C., Singletary, S. E., Hunt, K. K., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1345 · Cited by 474 · see citing works
Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer
Bear, H. D., Tang, G., Rastogi, P., Geyer, C. E., Robidoux, A., Atkins, J. N., Báez-Díaz, L., Brufsky, A., Mehta, R. S., Fehrenbacher, L., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1111097 · Cited by 460 · see citing works
Induction Chemoradiation and Surgical Resection for Superior Sulcus Non–Small-Cell Lung Carcinomas: Long-Term Results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160)
Rusch, V. W., Giroux, D. J., Kraut, M., Crowley, J. J., Hazuka, M. B., Winton, T. L., Johnson, D. H., Shulman, L. N., Shepherd, F. A., Deschamps, C. C., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.08.2826 · Cited by 458 · see citing works
Self-citation
Mediastinal Lymph Node Clearance After Docetaxel-Cisplatin Neoadjuvant Chemotherapy Is Prognostic of Survival in Patients With Stage IIIA pN2 Non–Small-Cell Lung Cancer: A Multicenter Phase II Trial
Betticher, D. C., Schmitz, S. H., Tötsch, M., Hansen, E., Joss, C., von Briel, C., Schmid, R. A., Pless, M., Habicht, J. M., Roth, A. D., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.11.040 · Cited by 449 · see citing works
Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657
Esserman, L. J., Berry, D. A., DeMichele, A. M., Carey, L., Davis, S., Buxton, M., Hudis, C., Gray, J. W., Perou, C. M., Yau, C. S. F., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.39.2779 · Cited by 439 · see citing works
Preoperative Chemotherapy Plus Surgery Versus Surgery Plus Adjuvant Chemotherapy Versus Surgery Alone in Early-Stage Non–Small-Cell Lung Cancer
Felip, E., Rosell, R., Maestre, J., Rodríguez-Paniagua, J. M., Morán, T., Astudillo, J., Alonso, G., Borro, J. M., González-Larriba, J. L., Torres, A., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.6204 · Cited by 431 · see citing works
Histopathologic Response Criteria Predict Survival of Patients with Resected Lung Cancer After Neoadjuvant Chemotherapy
Pataer, A., Kalhor, N., Correa, A. M., Raso, M. G., Erasmus, J. J., Kim, E. S., Behrens, C., Lee, J. J., Roth, J. A., Stewart, D. J., et al. (2012) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318247504a · Cited by 374 · see citing works
Self-citation
Preoperative chemotherapy for stage IIIa (N2) lung cancer: The Sloan-Kettering experience with 136 patients
Martini, N., Kris, M. G., Flehinger, B. J., Gralla, R. J., Bains, M. S., BURT, M. E., Heelan, R. T., McCormack, P. M. E., Pisters, K. M. W., Rigas, J. R., et al. (1993) · The Annals of Thoracic Surgery · doi:10.1016/0003-4975(93)91072-u · Cited by 371 · see citing works
Self-citation
Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer
Thomas, M., Rübe, C., Hoffknecht, P., et al. (2008) · The Lancet Oncology · doi:10.1016/s1470-2045(08)70156-6 · Cited by 347 · see citing works
Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review
GILLIGAN, D. M., Nicolson, M. C., Smith, I., et al. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60714-4 · Cited by 324 · see citing works
Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer.
Choi, N. C., Carey, R. W., Daly, W. J., et al. (1997) · Journal of Clinical Oncology · doi:10.1200/jco.1997.15.2.712 · Cited by 273 · see citing works
Randomized Phase III Study of Surgery Alone or Surgery Plus Preoperative Cisplatin and Gemcitabine in Stages IB to IIIA Non–Small-Cell Lung Cancer
Scagliotti, G. V., Pastorino, U., Vansteenkiste, J., Spaggiari, L., Facciolo, F., Orlowski, T. M., Maiorino, L., Hetzel, M., Leschinger, M. I., Visseren‐Grul, C., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.7089 · Cited by 272 · see citing works
Nodal stage after induction therapy for stage IIIA lung cancer determines patient survival
Bueno, R., Richards, W. G., Swanson, S., Jaklitsch, M. T., Lukanich, J. M., Mentzer, S. J., & Sugarbaker, D. J. (2000) · The Annals of Thoracic Surgery · doi:10.1016/s0003-4975(00)01585-x · Cited by 248 · see citing works
Surgery With or Without Preoperative Paclitaxel and Carboplatin in Early-Stage Non–Small-Cell Lung Cancer: Southwest Oncology Group Trial S9900, an Intergroup, Randomized, Phase III Trial
Pisters, K. M. W., Vallières, E., Crowley, J. J., Franklin, W. A., Bunn, P. A., Ginsberg, R. J., Putnam, J. B., Chansky, K., & Gandara, D. R. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.1685 · Cited by 247 · see citing works
Self-citation
Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data
Mauguen, A., Pignon, J., Burdett, S., Domerg, C., Fisher, D. J., Paulus, R., Mandrekar, S. J., Belani, C. P., Shepherd, F. A., Eisen, T. G., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70158-x · Cited by 245 · see citing works
Survival Benefit of Neoadjuvant Chemotherapy in Non-small Cell Lung Cancer: An Updated Meta-Analysis of 13 Randomized Control Trials
Song, W., Zhou, N., Wang, W., Chu, X., Liang, C.-Y., Tian, X., Guo, J., Liu, X., Liu, Y., & Dai, W.-M. (2010) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3181cd3345 · Cited by 216 · see citing works
Phase II Trial of Preoperative Chemoradiotherapy Followed by Surgical Resection in Patients With Superior Sulcus Non–Small-Cell Lung Cancers: Report of Japan Clinical Oncology Group Trial 9806
Kunitoh, H., Kato, H., Tsuboi, M., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.1911 · Cited by 212 · see citing works
Neoadjuvant chemotherapy and radiotherapy followed by surgery in stage IIIA non-small-cell carcinoma of the lung: report of a Cancer and Leukemia Group B phase II study.
Strauss, G. M., Herndon, J. E., Sherman, D. D., Mathisen, D. J., Carey, R. W., Choi, N. C., Rege, V. B., Modeas, C., & Green, M. R. (1992) · Journal of Clinical Oncology · doi:10.1200/jco.1992.10.8.1237 · Cited by 210 · see citing works
Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study
Betticher, D. C., Schmitz, S.-F. H., Tötsch, M., et al. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603075 · Cited by 207 · see citing works
Preoperative versus Postoperative Chemotherapy in Patients with Resectable Non-small Cell Lung Cancer: Systematic Review and Indirect Comparison Meta-Analysis of Randomized Trials
Lim, E. K. S., Harris, G., Patel, A. N., Adachi, I., Edmonds, L., & Song, F. (2009) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3181b9ecca · Cited by 201 · see citing works
A Systematic Review and Meta-analysis of the Literature: Chemotherapy and Surgery versus Surgery Alone in Non-small Cell Lung Cancer
Burdett, S., Stewart, L. A., & Rydzewska, L. H. M. (2006) · Journal of Thoracic Oncology · doi:10.1097/01243894-200609000-00003 · Cited by 199 · see citing works
Long-term results of combined-modality therapy in resectable non-small-cell lung cancer.
Martin, J., Ginsberg, R. J., Venkatraman, E. S., Bains, M. S., Downey, R. J., Korst, R. J., Kris, M. G., & Rusch, V. W. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.08.092 · Cited by 195 · see citing works
Self-citation
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Nagai, K., Tsuchiya, R., Mori, T., et al. (2003) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1067/mtc.2003.15 · Cited by 187 · see citing works
Preoperative chemotherapy and irradiation for stage III non-small cell lung cancer
Faber, L. P., Kittle, C. F., Warren, W. H., Bonomi, P., Taylor, S. G., Reddy, S., & Lee, M.-S. (1989) · The Annals of Thoracic Surgery · doi:10.1016/0003-4975(89)90115-x · Cited by 184 · see citing works
A systematic review and meta-analysis of the literature: chemotherapy and surgery versus surgery alone in non-small cell lung cancer.
Burdett, S., Stewart, L. A., & Rydzewska, L. H. M. (2006) · PubMed · Cited by 176 · see citing works
Grading of Tumor Regression in Non-small Cell Lung Cancer
Junker, K., Langner, K., Klinke, F., Bosse, U., & Thomas, M. (2001) · CHEST Journal · doi:10.1378/chest.120.5.1584 · Cited by 176 · see citing works
Tumour regression in non-small-cell lung cancer following neoadjuvant therapy. Histological assessment
Junker, K., Thomas, M., Schulmann, K., Klinke, F., Bosse, U., & M�ller, K.-M. (1997) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/bf01192200 · Cited by 174 · see citing works
Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study
Ciani, O., Buyse, M. E., Garside, R., Pavey, T., Stein, K., Sterne, J. A. C., & Taylor, R. S. (2013) · BMJ · doi:10.1136/bmj.f457 · Cited by 164 · see citing works
A perfect correlate does not a surrogate make
Baker, S. G., & Kramer, B. S. (2003) · BMC Medical Research Methodology · doi:10.1186/1471-2288-3-16 · Cited by 158 · see citing works
Computed Tomography RECIST Assessment of Histopathologic Response and Prediction of Survival in Patients with Resectable Non-Small Cell Lung Cancer after Neoadjuvant Chemotherapy
William, W. N., Pataer, A., Kalhor, N., Correa, A. M., Rice, D. C., Wistuba, I. I., Heymach, J., Lee, J. J., Kim, E. S., Munden, R., et al. (2013) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3182774108 · Cited by 138 · see citing works
Self-citation
Pathologic Complete Response to Preoperative Chemotherapy Predicts Cure in Early-Stage Non–Small-Cell Lung Cancer: Combined Analysis of Two IFCT Randomized Trials
Mouillet, G., Monnet, É., Milleron, B. J., Puyraveau, M., Quoix, É., David, P., Ducoloné, A., Molinier, O., Zalcman, G., Depierre, A., et al. (2012) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31824c7d92 · Cited by 134 · see citing works
A phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapy before surgery in patients with pathologically confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903)
Katakami, N., Tada, H., Mitsudomi, T., et al. (2012) · Cancer · doi:10.1002/cncr.26689 · Cited by 129 · see citing works
Phase II Trial of Neoadjuvant Bevacizumab Plus Chemotherapy and Adjuvant Bevacizumab in Patients with Resectable Nonsquamous Non–Small-Cell Lung Cancers
Chaft, J. E., Rusch, V., Ginsberg, M. S., Paik, P. K., Finley, D. J., Kris, M. G., Price, K. A. R., Azzoli, C. G., Fury, M. G., Riely, G. J., et al. (2013) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31829923ec · Cited by 122 · see citing works
Self-citation
Pathologic complete response in advanced non-small-cell lung cancer following preoperative chemotherapy: implications for the design of future non-small-cell lung cancer combined modality trials.
Pisters, K. M., Kris, M. G., Gralla, R. J., Zaman, M. B., Heelan, R. T., & Martini, N. (1993) · Journal of Clinical Oncology · doi:10.1200/jco.1993.11.9.1757 · Cited by 122 · see citing works
Self-citation
COMBINED RADIOTHERAPY AND RESECTION FOR CARCINOMA OF THE BRONCHUS EXPERIENCES WITH 66 PATIENTS
Bromley, L. L., & Szur, L. (1955) · The Lancet · doi:10.1016/s0140-6736(55)92787-2 · Cited by 106 · see citing works
Pathologic complete response in advanced non-small-cell lung cancer following preoperative chemotherapy: Implications for the design of future non-small-cell lung cancer combined modality trials
Pisters, K. M. W. (1994) · Lung Cancer · doi:10.1016/0169-5002(94)90385-9 · Cited by 106 · see citing works
Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer
Bear, H. D., Tang, G., Rastogi, P., et al. (2013) · Obstetrical & Gynecological Survey · doi:10.1097/ogx.0b013e3182877729 · Cited by 81 · see citing works
Abstract P1-14-20: Meta-analysis Results from the Collaborative Trials in Neoadjuvant Breast Cancer (CTNeoBC)
Cortazar, P., Zhang, L., Untch, M., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.sabcs12-p1-14-20 · Cited by 79 · see citing works
Nodal downstaging predicts survival following induction chemotherapy for stage IIIA (N2) non-small cell lung cancer in CALGB protocol #8935
Jaklitsch, M. T., Herndon, J. E., DeCamp, M. M., Richards, W. G., Kumar, P., Krasna, M. J., Green, M. R., & Sugarbaker, D. J. (2006) · Journal of Surgical Oncology · doi:10.1002/jso.20644 · Cited by 59 · see citing works
Abstract S1-11: Meta-analysis Results from the Collaborative Trials in Neoadjuvant Breast Cancer (CTNeoBC)
Cortazar, P., Zhang, L., Untch, M., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.sabcs12-s1-11 · Cited by 46 · see citing works
Preoperative Chemotherapy (Cisplatin and Fluorouracil) and Radiation Therapy in Stage III Non-small Cell Lung Cancer
Weiden, P. L., & Piantadosi, S. (1994) · CHEST Journal · doi:10.1378/chest.106.6_supplement.344s · Cited by 34 · see citing works
Neoadjuvant Chemotherapy With Docetaxel-Cisplatin in Patients With Stage III N2 Non–Small-Cell Lung Cancer
Liao, W., Chen, J.-H., Wu, M., et al. (2013) · Clinical Lung Cancer · doi:10.1016/j.cllc.2012.10.003 · Cited by 31 · see citing works
Neoadjuvant chemotherapy with or without preoperative irradiation in stage IIIA/N2 non-small cell lung cancer (NSCLC): A randomized phase III trial by the Swiss Group for Clinical Cancer Research (SAKK trial 16/00).
Pless, M., Stupp, R., Ris, H., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.31.15_suppl.7503 · Cited by 19 · see citing works
Preoperative chemotherapy (cisplatin and fluorouracil) and radiation therapy in stage III non-small cell lung cancer. A phase 2 study of the LCSG
Weiden, P. L., & Piantadosi, S. (1994) · CHEST Journal · doi:10.1378/chest.106.6.344s · Cited by 18 · see citing works
Results of the IFCT 0002 phase III study comparing a preoperative and a perioperative chemotherapy (CT) with two different CT regimens in resectable non-small cell lung cancer (NSCLC)
Westeel, V., Milleron, B. J., Quoix, É., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.15_suppl.7530 · Cited by 16 · see citing works
CHRONIC BRONCHITIS AND SMOKING
Corfield, C. (1957) · The Lancet · doi:10.1016/s0140-6736(57)91270-9 · Cited by 5 · see citing works

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Authors: Hellmann, M. D., Chaft, J. E., William, W. N., Rusch, V., Pisters, K. M. W., Kalhor, N., Pataer, A., Travis, W. D., Swisher, S. G., & Kris, M. G.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
The University of Texas MD Anderson Cancer Center (US)
Corresponding author: Kris, Mark G
ORCID: Hellmann, Matthew D
Chaft, Jamie E
William, William N
Rusch, Valerie
Kalhor, Neda
Pataer, Apar
Travis, William D
Swisher, Stephen G
Kris, Mark G
Venue: The Lancet Oncology
Publisher: Elsevier BV
Published: 2014-01
Volume: 15
Issue: 1
Pages: e42-e50
ISSN: 1470-2045 (ISSN-L)
DOI: 10.1016/s1470-2045(13)70334-6
PMC: PMC4734624
OpenAlex: W2134291074
Cited by: 646
References: 81
Citations by year: 2026: 64 · 2025: 77 · 2024: 84 · 2023: 111 · 2022: 98 · 2021: 84 · 2020: 46 · 2019: 26 · 2018: 26 · 2017: 9 · 2016: 8 · 2015: 10 · 2014: 2
FWCI: 1.65
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: The Lancet Oncology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (P30CA008748, P30CA016672)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords: non-small cell lung cancer, neoadjuvant chemotherapy, major pathological response, surrogate endpoints, resectable lung cancer, overall survival, clinical trial design, treatment response
MeSH terms: Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Neoplasm Staging, Biomarkers, Neoadjuvant Therapy

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Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint

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