Negative hyper-selection of metastatic colorectal cancer patients for anti-EGFR monoclonal antibodies: the PRESSING case-control study Ann. Oncol. (IF 11.855) Pub Date : 2017-09-25 C. Cremolini, F. Morano, R. Moretto, R. Berenato, E. Tamborini, F. Perrone, D. Rossini, A. Gloghini, A. Busico, G. Zucchelli, C. Baratelli, E. Tamburini, M. Tampellini, E. Sensi, G. Fucà, C. Volpi, M. Milione, M. Di Maio, G. Fontanini, F. De Braud, A. Falcone, F. Pietrantonio
Refining the selection of metastatic colorectal cancer (mCRC) patients candidates for anti-EGFR monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signaling pathways, have been suggested by preclinical and retrospective studies.
LAG-3+ tumor infiltrating lymphocytes in breast cancer: clinical correlates and association with PD-1/PD-L1+ tumors Ann. Oncol. (IF 11.855) Pub Date : 2017-09-25 S. Burugu, D. Gao, S. Leung, S. K. Chia, T.O. Nielsen
Background: Novel immune checkpoint blockade strategies are being evaluated in clinical trials and include targeting the lymphocyte activation gene 3 (LAG-3) checkpoint, alone or in combination with PD-1/PD-L1 blockade. We investigated LAG-3 expression and its prognostic value in a large series of breast cancer patients, and correlated LAG-3 expression with key biomarkers including PD-1 and PD-L1.
Gemcitabine plus sirolimus for relapsed and progressing osteosarcoma patients after standard chemotherapy: a multicenter, single-arm phase II trial of Spanish Group for Research on Sarcoma (GEIS). Ann. Oncol. (IF 11.855) Pub Date : 2017-09-25 J. Martin-Broto, A. Redondo, C. Valverde, M.A. Vaz, J. Mora, X. Garcia del Muro, A. Gutierrez, C. Tous, A. Carnero, D. Marcilla, A. Carranza, P. Sancho, J. Martinez-Trufero, R. Diaz-Beveridge, J. Cruz, V. Encinas, M. Taron, D. S. Moura, P. Luna, N. Hindi, A. Lopez-Pousa
Patients with relapsed unresectable osteosarcoma represents an unmet need, so active and safe systemic treatments are required. FAS and mTOR pathways are implicated in progressing osteosarcoma, and we had preclinical and clinical experience with a scheme that targets both pathways. Therefore, we designed a phase II trial with gemcitabine plus rapamycin, to determine the efficacy and safety, in this subset of patients.
The antibody-drug conjugate target landscape across a broad range of tumour types Ann. Oncol. (IF 11.855) Pub Date : 2017-09-25 K. L. Moek, D. J. A. de Groot, E. G. E. de Vries, R. S. N. Fehrmann
Antibody-drug conjugates (ADCs), consisting of an antibody designed against a specific target at the cell membrane linked with a cytotoxic agent, are an emerging class of therapeutics. Since ADC tumour cell targets do not have to be drivers of tumour growth, ADCs are potentially relevant for a wide range of tumours currently lacking clear oncogenic drivers. Therefore, we aimed to define the landscape of ADC targets in a broad range of tumours.
Surfaceome profiling enables isolation of cancer-specific exosomal cargo in liquid biopsies from pancreatic cancer patients Ann. Oncol. (IF 11.855) Pub Date : 2017-09-25 J. Castillo, V. Bernard, F. A. San Lucas, K. Allenson, M. Capello, D. U. Kim, P. Gascoyne, F. C. Mulu, B. M. Stephens, J. Huang, H. Wang, A. A. Momin, R. O. Jacamo, M. Katz, R. Wolff, M. Javle, G. Varadhachary, I. I. Wistuba, S. Hanash, A. Maitra, H. Alvarez
Detection of circulating tumor DNA (ctDNA) can be limited due to their relative scarcity in circulation, particularly while patients are actively undergoing therapy. Exosomes provide a vehicle through which cancer-specific material can be enriched from the compendium of circulating non-neoplastic tissue-derived nucleic acids. We performed a comprehensive profiling of the pancreatic ductal adenocarcinoma (PDAC) exosomal “surfaceome” in order to identify surface proteins that will render liquid biopsies amenable to cancer-derived exosome enrichment for downstream molecular profiling.
Mechanisms regulating T-cell infiltration and activity in solid tumors Ann. Oncol. (IF 11.855) Pub Date : 2017-09-21 E. Lanitis, D. Dangaj, M. Irving, G. Coukos
T-lymphocytes play a critical role in cancer immunity as evidenced by their presence in resected tumor samples derived from long-surviving patients, and impressive clinical responses to various immunotherapies that reinvigorate them. Indeed, tumors can upregulate a wide array of defense mechanisms, both direct and indirect, to suppress the ability of Tcells to reach the tumor bed and mount curative responses upon infiltration. In addition, patient and tumor genetics, previous antigenic experience, and the microbiome, are all important factors in shaping the T-cell repertoire and sensitivity to immunotherapy. Here, we review the mechanisms that regulate T-cell homing, infiltration, and activity within the solid tumor bed. Finally, we summarize different immunotherapies and combinatorial treatment strategies that enable the immune system to overcome barriers for enhanced tumor control and improved patient outcome.
Allogeneic Hematopoietic Cell Transplantation in Intermediate Risk Acute Myeloid Leukemia negative for FLT3-ITD, NPM1- or biallelic CEBPA Mutations Ann. Oncol. (IF 11.855) Pub Date : 2017-09-01 K. Heidrich, C. Thiede, K. Schäfer-Eckart, N. Schmitz, W. E. Aulitzky, A. Krämer, W. Rösler, M. Hänel, H. Einsele, C. D. Baldus, R. U. Trappe, F. Stölzel, J. M. Middeke, C. Röllig, F. Taube, M. Kramer, H. Serve, W. E. Berdel, G. Ehninger, M. Bornhäuser, J. Schetelig
The value of allogeneic hematopoietic cell transplantation (alloHCT) as postremission treatment is not well defined for patients with intermediate-risk acute myeloid leukemia (AML) without FLT3-ITD, biallelic CEBPA-, or NPM1 mutations (here referred to as NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg AML) in first complete remission (CR1).
Borealis-1: A Randomized, First Line, Placebo-Controlled Phase 2 Study Evaluating Apatorsen and Chemotherapy for Patients with Advanced Urothelial Cancer Ann. Oncol. (IF 11.855) Pub Date : 2017-07-24 J. Bellmunt, B. J. Eigl, E. Senkus, Y. Loriot, P. Twardowski, D. Castellano, N. Blais, S. S. Sridhar, C. N. Sternberg, M. Retz, S. Pal, B. Blumenstein, C. Jacobs, P. S. Stewart, D. Petrylak
Five-year survival of patients with inoperable, advanced urothelial carcinoma treated with the first-line chemotherapy is 5%–15%. We assessed whether the Hsp27 inhibitor apatorsen combined with gemcitabine plus cisplatin (GC) could improve overall survival (OS) in these patients.
Dual MET and ERBB inhibition overcomes intra-tumor plasticity in osimertinib resistant advanced non-small cell lung cancer (NSCLC) Ann. Oncol. (IF 11.855) Pub Date : 2017-07-21 A. Martinez-Marti, E. Felip, J. Matito, E. Mereu, A. Navarro, S. Cedrés, N. Pardo, A. Martinez de Castro, J. Remon, JM. Miquel, A. Guillaumet-Adkins, E. Nadal, G. Rodriguez-Esteban, O. Arqués, R. Fasani, P. Nuciforo, H. Heyn, A. Villanueva, H. G. Palmer, A. Vivancos
Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as osimertinib are the last line of targeted treatment of metastatic non-small-cell lung cancer (NSCLC) EGFR-mutant harboring T790M. Different mechanisms of acquired resistance to third-generation EGFR-TKIs have been proposed. It is therefore crucial to identify new and effective strategies to overcome successive acquired mechanisms of resistance.
Whole Brain Radiotherapy after Stereotactic Radiosurgery or Surgical Resection among Patients with 1-3 Brain Metastases and Favorable Prognoses: A Secondary Analysis of EORTC 22952-26001. Ann. Oncol. (IF 11.855) Pub Date : 2017-06-27 T. M. Churilla, E. Handorf, S. Collette, L. Collette, Y. Dong, A. A. Aizer, M. Kocher, R. Soffietti, B. M. Alexander, S. E. Weiss
The absence of a survival benefit for whole brain radiotherapy (WBRT) among randomized trials has been attributed to a competing risk of death from extracranial disease. We re-analyzed EORTC 22952 to assess the impact of WBRT on survival for patients with controlled extracranial disease or favorable prognoses.
Overall survival analysis of EXAM, a phase 3 trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma Ann. Oncol. (IF 11.855) Pub Date : 2017-09-22 M. Schlumberger, R. Elisei, S. Müller, P. Schöffski, M. Brose, M. Shah, L. Licitra, J. Krajewska, M. C. Kreissl, B. Niederle, E. E. W. Cohen, L. Wirth, H. Ali, D. O. Clary, Y. Yaron, M. Mangeshkar, D. Ball, B. Nelkin, S. Sherman
Primary analysis of the double-blind, phase 3 EXAM trial demonstrated significant improvement in progression-free survival (PFS) with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was performed after long-term follow-up.
Phase II randomized trial of carboplatin, paclitaxel, bevacizumab with or without cixutumumab (IMC-A12) in patients with advanced non-squamous, non-small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E3508) Ann. Oncol. (IF 11.855) Pub Date : 2017-09-18 A. Argiris, J.W. Lee, J. Stevenson, M.G. Sulecki, V. Hugec, N.W. Choong, J.N. Saltzman, W. Song, R.M. Hansen, T.L. Evans, S.S. Ramalingam, J.H. Schiller
Background: Cixutumumab is a fully human IgG1 monoclonal antibody to the insulin-like growth factor type I receptor (IGF-IR) that can potentially reverse resistance and enhance the efficacy of chemotherapy.
A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study Ann. Oncol. (IF 11.855) Pub Date : 2017-09-18 V Chajès, N Assi, C Biessy, P Ferrari, S Rinaldi, N Slimani, GM Lenoir, L Baglietto, M His, MC Boutron-Ruault, A Trichopoulou, P Lagiou, M Katsoulis, R Kaaks, T Kühn, S Panico, V Pala, G Masala, H.B Bueno-de-Mesquita, PH Peeters, C van Gils, A Hjartåker, Standahl K Olsen, Borgund R Barnung, A Barricarte, D Redondo- Sanchez, V Menéndez, P Amiano, M Wennberg, T Key, KT Khaw, MA Merritt, E Riboli, MJ Gunter, I Romieu
Background Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting.
Successful targeting of the NRG1 pathway indicates novel treatment strategy for metastatic cancer Ann. Oncol. (IF 11.855) Pub Date : 2017-09-18 M. R. Jones, H. Lim, Y. Shen, E. Pleasance, C. Ch'ng, C. Reisle, S. Leelakumari, C. Zhao, S. Yip, J. Ho, E. Zhong, T. Ng, D. Ionescu, D.F. Schaeffer, A. J. Mungall, K. L. Mungall, Y. Zhao, R. A. Moore, Y. Ma, S Chia, C. Ho, D. J. Renouf, K. Gelmon, S. J. M. Jones, M. A. Marra, J. Laskin
The predictive role of interim PET after the first chemotherapy cycle and sequential evaluation of response to ABVD in Hodgkin lymphoma patients - the Polish Lymphoma Research Group (PLRG) Observational Study Ann. Oncol. (IF 11.855) Pub Date : 2017-09-18 J.M. Zaucha, B. Małkowski, S. Chauvie, Subocz E., J. Tajer, Kulikowski W., A. Fijołek-Warszewska, A. Biggi, F. Fallanca, M. Kobylecka, M. Dziuk, D. Woszczyk, J. Rybka, R. Kroll-Balcerzak, F. Bergesio, A. Romanowicz, A Chamier-Ciemińska, P. Kurczab, A. Giza, K. Leśniewski-Kmak, R. Zaucha, D. Świetlik, T. Wróbel, W. Knopińska-Posłuszny, J. Walewski, A. Gallamini
Background: Interim PET after 2 ABVD cycles (iPET2) predicts treatment outcome in classical Hodgkin lymphoma (cHL). To test if an earlier assessment of chemosensitivity would improve the prediction accuracy, we launched a prospective, multicenter observational study aimed at assessing the predictive value (PV) of iPET after 1 ABVD (iPET1) and the kinetics of response assessed by sequential PET scanning.
Adjuvant Chemotherapy in Patients with Stage I Endometrioid or Clear Cell Ovarian Cancer in the Platinum Era: A Surveillance, Epidemiology, and End Results Cohort Study, 2000-2013 Ann. Oncol. (IF 11.855) Pub Date : 2017-09-18 A. Oseledchyk, M. M. Leitao, J. Konner, R. E. O’Cearbhaill, D. Zamarin, Y. Sonoda, G. J. Gardner, K. Long Roche, C. A. Aghajanian, R. N. Grisham, C. L. Brown, A. Snyder, D. S. Chi, R. A. Soslow, N. R. Abu-Rustum, O. Zivanovic
Background: We sought to evaluate the impact of adjuvant chemotherapy on overall survival (OS) in patients with stage I endometrioid epithelial ovarian cancer (EEOC) or ovarian clear cell cancer (OCCC) using a national database.
Activity and safety of crizotinib in patients with advanced clear cell sarcoma with MET alterations. European Organization for Research and Treatment of Cancer phase 2 trial 90101 “CREATE” Ann. Oncol. (IF 11.855) Pub Date : 2017-09-18 P. Schöffski, A. Wozniak, P. G. Casali, P. Rutkowski, J-Y. Blay, L. H. Lindner, S. J. Strauss, A. Anthoney, F. Duffaud, S. Richter, V. Grünwald, M. G. Leahy, P. Reichardt, J. Sufliarsky, W. T. van der Graaf, R. Sciot, M. Debiec-Rychter, T. van Cann, S. Marréaud, M. Lia, T. Raveloarivahy, L. Collette, S. Bauer
Background: Clear cell sarcoma (CCSA) is an orphan malignancy, characterised by a specific t(12;22) translocation, leading to rearrangement of the EWSR1 gene and overexpression of MET. We prospectively investigated the efficacy and safety of the tyrosine kinase inhibitor (TKI) crizotinib in patients with advanced or metastatic CCSA.
Maintenance therapy in advanced colorectal cancer, yes or no? Ask the laboratory Ann. Oncol. (IF 11.855) Pub Date : 2017-08-02 A. Sobrero, A. Damiani
In oncology, the concept of maintenance therapy is dependent upon two conditions: the availability of an effective induction treatment preventing a rapid progression and a certain degree of toxicity that does not allow indefinite continuation of therapy. When FU was the only active agent against advanced colorectal cancer we knew that continuing FU chemotherapy beyond 3–5 months (the time to response and maximum response to this agent) was not efficacious . When FOLFOX and FOLFIRI became standard practice (prolongation of median OS beyond 18 months, but added toxicity), investigating less intense ways of prolonging the first line treatment became necessary. Consequently, the on–off FOLFIRI strategy  and the intermittent use of oxaliplatin  were demonstrated to be equivalent...
Metastasis of cancer: when and how? Ann. Oncol. (IF 11.855) Pub Date : 2017-07-08 W.-C. Lee, S. Kopetz, I. I. Wistuba, J. Zhang
Despite encouraging advances in both local and systemic treatment over the past two decades, cancer remains the leading cause of death worldwide. Metastasis, a process of cancer cells spreading from the primary tumor to surrounding tissues and to distant organs is the primary cause of cancer mortality. It is estimated that metastasis is responsible for ∼90% of cancer deaths . This has not changed much in the past half century . Understanding metastases is critical to improving cancer patient outcomes. Although metastasis equates to late stage cancer clinically, when the process begins and how metastasis occurs is largely unknown.
Revival of PI3K inhibitors in non-Hodgkin’s lymphoma Ann. Oncol. (IF 11.855) Pub Date : 2017-07-18 C. L. Batlevi, A. Younes
The phosphoinositide 3-kinase (PI3K) family is classified into three distinct classes (I, II and III). Class I is most relevant to cell growth and survival and has been the target for drug development of cancer. The class I PI3K pathway includes four isoforms: α, β, δ, and γ . PI3Kδ and -γ expression is largely limited to leukocytes, while PI3K-α and -β are ubiquitously expressed . PI3Kα mutations and amplifications have been identified across multiple cancer subtypes and both overexpression of PI3Kα and gain of function PI3Kα mutations were found to be oncogenic [3–6]. PI3Kα is also the primary isoform required for insulin signaling . PI3Kβ isoform has roles in regulating formation and stability of integrin...
Proton therapy in mediastinal Hodgkin lymphoma: moving from dosimetric prediction to clinical evidence Ann. Oncol. (IF 11.855) Pub Date : 2017-07-14 U. Ricardi, B. Dabaja, D. C. Hodgson
Combined modality therapy with chemotherapy followed by consolidation radiotherapy is now considered the standard of care in early-stage Hodgkin lymphoma (HL); in advanced stage disease with bulky sites, radiotherapy may also be used to locally consolidate response after more intensive chemotherapy . As most early-stage HL patients achieve durable complete remission and become long-term survivors, it is important to reduce the risk of treatment-induced late effects . This is especially relevant for patients with mediastinal involvement as their disease is in close proximity to critical healthy tissues (heart, lungs, breasts). The effort to reduce treatment-related toxicity—mainly cardiovascular disease and secondary malignancies—is the main driver behind the recent improvements in the radiation therapy (RT) delivery for patients with HL.
The Italian Collaborative Group sets a standard for the treatment of locally advanced head and neck cancer Ann. Oncol. (IF 11.855) Pub Date : 2017-07-28 K. Misiukiewicz, V. Gupta, M. Posner
The role of induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head/neck (LA-SCCHN) continues to be a controversial. While randomized trials have established that cisplatin/5-FU (PF) IC is equivalent to surgery followed by radiation therapy and may improve survival compared with chemoradiotherapy (CRT) for organ preservation, a definitive answer in locally advanced disease, outside of organ preservation, has been elusive [1–3]. The DeCIDE and Paradigm trials are considered to be negative IC trials exploring taxotere/cisplatin/5-FU (TPF) as IC, however both trials were inconclusive. They accrued poorly and failed to meet planned enrollment goals. Hence, the studies were underpowered and the results indeterminate [4, 5]. The GSTTC Italian Collaborative Group study in this issue of the Annals...
Chemotherapy-induced toxicity—a secondary effect caused by released DNA? Ann. Oncol. (IF 11.855) Pub Date : 2017-07-13 T. Helleday
The use of chemotherapy treatment is often limited by toxic side-effects caused to healthy cells. In general, most chemotherapy treatments cause DNA damage or stop cells in mitosis, targeting both dividing cancer and dividing healthy cells (e.g. gut epithelium, bone marrow, hair follicle). Clearly, DNA damaging chemotherapy treatments may cause damage to both cancer and healthy cells to generate toxic side-effects (Figure 1A). In a new study presented in this issue of Annals of Oncology, Mittra et al. challenge this concept and suggest that released cell-free chromatin (cfCh) may itself cause inflammation and DNA damage as a secondary event  (Figure 1B). The authors also demonstrate that treatment with DNAse I or the DNA-degrading agent Resveratrol-Cu may suppress some...
Treating cancer cachexia: an evolving landscape Ann. Oncol. (IF 11.855) Pub Date : 2017-07-11 B. Laird, M. Fallon
Currently, there is no licensed treatment and no standard of care for cancer cachexia. Putting this in the context of a condition which impairs the delivery of anti-cancer therapy (through increased side-effects, treatment delays, dose reductions) , causes marked distress to patients and their families and is associated with reduced survival, there remains an urgency to progress the research agenda in cancer cachexia .
The ‘critical mass’ survey of palliative care programme at ESMO designated centres of integrated oncology and palliative care Ann. Oncol. (IF 11.855) Pub Date : 2017-07-19 D. Hui, N. Cherny, N. Latino, F. Strasser
The ESMO Designated Centres (ESMO-DCs) of Integrated Oncology and Palliative Care (PC) Incentive Programme has grown steadily. We aimed to characterise the level of PC clinical services, education and research at ESMO-DCs.
Borderline resectable pancreatic cancer: conceptual evolution and current approach to image-based classification Ann. Oncol. (IF 11.855) Pub Date : 2017-04-12 J. W. Gilbert, B. Wolpin, T. Clancy, J. Wang, H. Mamon, A. B. Shinagare, J. Jagannathan, M. Rosenthal
Diagnostic imaging plays a critical role in the initial diagnosis and therapeutic monitoring of pancreatic adenocarcinoma. Over the past decade, the concept of ‘borderline resectable’ pancreatic cancer has emerged to describe a distinct subset of patients existing along the spectrum from resectable to locally advanced disease for whom a microscopically margin-positive (R1) resection is considered relatively more likely, primarily due to the relationship of the primary tumor with surrounding vasculature.
How health-related quality of life assessment should be used in advanced colorectal cancer clinical trials Ann. Oncol. (IF 11.855) Pub Date : 2017-04-18 F. Bonnetain, C. Borg, R. R. Adams, J. A. Ajani, A. Benson, H. Bleiberg, B. Chibaudel, E. Diaz-Rubio, J. Y. Douillard, C. S. Fuchs, B. J. Giantonio, R. Goldberg, V. Heinemann, M. Koopman, R. Labianca, A. K. Larsen, T. Maughan, E. Mitchell, M. Peeters, C. J. A. Punt, H. J. Schmoll, C. Tournigand, A. de Gramont
Traditionally, the efficacy of cancer treatment in patients with advance or metastatic disease in clinical studies has been studied using overall survival and more recently tumor-based end points such as progression-free survival, measurements of response to treatment. However, these seem not to be the relevant clinical end points in current situation if such end points were no validated as surrogate of overall survival to demonstrate the clinical efficacy. Appropriate, meaningful, primary patient-oriented and patient-reported end points that adequately measure the effects of new therapeutic interventions are then crucial for the advancement of clinical research in metastatic colorectal cancer to complement the results of tumor-based end points. Health-related quality of life (HRQoL) is effectively an evaluation of quality of life and its relationship with health over time. HRQoL includes the patient report at least of the way a disease or its treatment affects its physical, emotional and social well-being. Over the past few years, several phase III trials in a variety of solid cancers have assessed the incremental value of HRQoL in addition to the traditional end points of tumor response and survival results. HRQoL could provide not only complementary clinical data to the primary outcomes, but also more precise predictive and prognostic value. This end point is useful for both clinicians and patients in order to achieve the dogma of precision medicine. The present article examines the use of HRQoL in phase III metastatic colorectal cancer clinical trials, outlines the importance of HRQoL assessment methods, analysis, and results presentation. Moreover, it discusses the relevance of including HRQoL as a primary/co-primary end point to support the progression-free survival results and to assess efficacy of treatment in the advanced disease setting.
International cancer seminars: a focus on esophageal squamous cell carcinoma Ann. Oncol. (IF 11.855) Pub Date : 2017-06-14 G. Murphy, V. McCormack, B. Abedi-Ardekani, M. Arnold, M. C. Camargo, N. A. Dar, S. M. Dawsey, A. Etemadi, R. C. Fitzgerald, D. E. Fleischer, N. D. Freedman, A. M. Goldstein, S. Gopal, M. Hashemian, N. Hu, P. L. Hyland, B. Kaimila, F. Kamangar, R. Malekzadeh, C. G. Mathew, D. Menya, G. Mulima, M. M. Mwachiro, A. Mwasamwaja, N. Pritchett, Y.-L. Qiao, L. F. Ribeiro-Pinto, M. Ricciardone, J. Schüz, F. Sitas, P. R. Taylor, K. Van Loon, S.-M. Wang, W.-Q. Wei, C. P. Wild, C. Wu, C. C. Abnet, S. J. Chanock, P. Brennan
The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) have initiated a series of cancer-focused seminars [Scelo G, Hofmann JN, Banks RE et al. International cancer seminars: a focus on kidney cancer. Ann Oncol 2016; 27(8): 1382–1385]. In this, the second seminar, IARC and NCI convened a workshop in order to examine the state of the current science on esophageal squamous cell carcinoma etiology, genetics, early detection, treatment, and palliation, was reviewed to identify the most critical open research questions. The results of these discussions were summarized by formulating a series of ‘difficult questions’, which should inform and prioritize future research efforts.
Unmet needs in the first-line treatment of follicular lymphoma Ann. Oncol. (IF 11.855) Pub Date : 2017-04-18 C. Casulo, L. Nastoupil, N. H. Fowler, J. W. Friedberg, C. R. Flowers
For the majority of patients with newly diagnosed follicular lymphoma (FL), current treatments, while not curative, allow for long remission durations. However, several important needs remain unaddressed. Studies have consistently shown that ∼20% of patients with FL experience disease progression within 2 years of first-line treatment, and consequently have a 50% risk of death in 5 years. Better characterization of this group of patients at diagnosis may provide insight into those in need of alternate or intensive therapies, facilitate a precision approach to inform clinical trials, and allow for improved patient counseling. Prognostic methods to date have employed clinical parameters, genomic methods, and a wide assortment of biological and biochemical markers, but none so far has been able to adequately identify this high-risk population. Advances in the first-line treatment of FL with chemoimmunotherapy have led to a median progression-free survival (PFS) of approximately 7 years; creating a challenge in the development of clinical trials where PFS is a primary end point. A surrogate end point that accurately predicts PFS would allow for new treatments to reach patients with FL sooner, or lessen toxicity, time, and expense to those patients requiring little to no therapy. Quality of response to treatment may predict PFS and overall survival in FL; as such complete response rates, either alone or in conjunction with PET imaging or minimal residual disease negativity, are being studied as surrogates, with complete response at 30 months after induction providing the strongest surrogacy evidence to date. A better understanding of how to optimize quality of life in the context of this chronic illness is another important focus deserving of further study. Ongoing efforts to address these important unmet needs are herein discussed.
Forcing the vicious circle: sarcopenia increases toxicity, decreases response to chemotherapy and worsens with chemotherapy Ann. Oncol. (IF 11.855) Pub Date : 2017-05-29 F. Bozzetti
Sarcopenia has recently emerged as a new condition that, independently from malnutrition, may adversely affect the prognosis of cancer patients. Purpose of this narrative review is to define the prevalence of sarcopenia in different primaries, its role in leading to chemotherapy toxicity and decreased compliance with the oncological therapy and the effect of some drugs on the onset of sarcopenia. Finally, the review aims to describe the current approaches to restore the muscle mass through nutrition, exercise and anti-inflammatory agents or multimodal programmes with a special emphasis on the results of randomized controlled trials. The examination of the computed tomography scan at the level of the third lumbar vertebra—a common procedure for staging many tumours—has allowed the oncologist to evaluate the muscle mass and to collect many retrospective data on the prevalence of sarcopenia and its clinical consequences. Sarcopenia is a condition affecting a high percentage of patients with a range depending on type of primary tumour and stage of disease. It is noteworthy that patients may be sarcopenic even if their nutritional status is apparently maintained or they are obese. Sarcopenic patients exhibited higher chemotherapy toxicity and poorer compliance with oncological treatments. Furthermore, several antineoplastic drugs appeared to worsen the sarcopenic status. Therapeutic approaches are several and this review will focus on those validated by randomized controlled trials. They include the use of ω-3-enriched oral nutritional supplements and orexigenic agents, the administration of adequate high-protein regimens delivered enterally or parenterally, and programmes of physical exercise. Better results are expected combining different procedures in a multimodal approach. In conclusion, there are several premises to prevent/treat sarcopenia. The oncologist should coordinate this multimodal approach by selecting priorities and sequences of treatments and then involving a nutrition health care professional or a physical therapist depending on the condition of the single patient.
Prevention of chemotherapy toxicity by agents that neutralize or degrade cell-free chromatin Ann. Oncol. (IF 11.855) Pub Date : 2017-06-23 I. Mittra, K. Pal, N. Pancholi, A. Shaikh, B. Rane, P. Tidke, S. Kirolikar, N. K. Khare, K. Agrawal, H. Nagare, N. K. Nair
Toxicity associated with chemotherapy is a major therapeutic challenge and is caused by chemotherapy-induced DNA damage and inflammation. We have recently reported that cell-free chromatin (cfCh) fragments released from dying cells can readily enter into healthy cells of the body to integrate into their genomes and induce DNA double-strand breaks, apoptosis and inflammation in them. We hypothesized that much of the toxicity of chemotherapy might be due to release of large quantities of cfCh from dying cells that could trigger an exaggerated DNA damage, apoptotic and inflammatory response in healthy cells over and above that caused by the drugs themselves.
Maintenance treatment with capecitabine and bevacizumab versus observation in metastatic colorectal cancer: updated results and molecular subgroup analyses of the phase 3 CAIRO3 study Ann. Oncol. (IF 11.855) Pub Date : 2017-06-23 K. K. H. Goey, S. G. Elias, H. van Tinteren, M. M. Laclé, S. M. Willems, G. J. A. Offerhaus, W. W. J. de Leng, E. Strengman, A. J. ten Tije, G.-J. M. Creemers, A. van der Velden, F. E. de Jongh, F. L. G. Erdkamp, B. C. Tanis, C. J. A. Punt, M. Koopman
The phase 3 CAIRO3 study showed that capecitabine plus bevacizumab (CAP-B) maintenance treatment after six cycles capecitabine, oxaliplatin, and bevacizumab (CAPOX-B) in metastatic colorectal cancer (mCRC) patients is effective, without compromising quality of life. In this post hoc analysis with updated follow-up and data regarding sidedness, we defined subgroups according to RAS/BRAF mutation status and mismatch repair (MMR) status, and investigated their influence on treatment efficacy.
Multiregion whole-exome sequencing of matched primary and metastatic tumors revealed genomic heterogeneity and suggested polyclonal seeding in colorectal cancer metastasis Ann. Oncol. (IF 11.855) Pub Date : 2017-07-19 Q. Wei, Z. Ye, X. Zhong, L. Li, C. Wang, R. E. Myers, J. P. Palazzo, D. Fortuna, A. Yan, S. A. Waldman, X. Chen, J. A. Posey, A. Basu-Mallick, B. H. Jiang, L. Hou, J. Shu, Y. Sun, J. Xing, B. Li, H. Yang
Distant metastasis accounts for 90% of deaths from colorectal cancer (CRC). Genomic heterogeneity has been reported in various solid malignancies, but remains largely under-explored in metastatic CRC tumors, especially in primary to metastatic tumor evolution.
A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer Ann. Oncol. (IF 11.855) Pub Date : 2017-08-03 J. A. Ajani, M. Abramov, I. Bondarenko, Y. Shparyk, V. Gorbunova, A. Hontsa, N. Otchenash, M. Alsina, S. Lazarev, J. Feliu, A. Elme, V. Esko, K. Abdalla, U. Verma, F. Benedetti, T. Aoyama, H. Mizuguchi, L. Makris, G. Rosati
The effect of histology-based treatment regimen on diffuse gastric adenocarcinoma has not been evaluated in clinical trials. This international phase III trial evaluated the efficacy and safety of S-1 (a contemporary oral fluoropyrimidine)/cisplatin versus 5-fluorouracil (5-FU)/cisplatin in chemotherapy-naïve patients with diffuse-type adenocarcinoma involving the gastroesophageal junction or stomach.
Clinical utility of circulating DNA analysis for rapid detection of actionable mutations to select metastatic colorectal patients for anti-EGFR treatment Ann. Oncol. (IF 11.855) Pub Date : 2017-06-30 A. R. Thierry, S. El Messaoudi, C. Mollevi, J. L. Raoul, R. Guimbaud, D. Pezet, P. Artru, E. Assenat, C. Borg, M. Mathonnet, C. De La Fouchardière, O. Bouché, C. Gavoille, C. Fiess, B. Auzemery, R. Meddeb, E. Lopez-Crapez, C. Sanchez, B. Pastor, M. Ychou
While tumor-tissue remains the ‘gold standard’ for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care.
Prediction of pathological response to neoadjuvant treatment in rectal cancer with a two-protein immunohistochemical score derived from stromal gene-profiling Ann. Oncol. (IF 11.855) Pub Date : 2017-07-06 S. Gonçalves-Ribeiro, R. Sanz-Pamplona, A. Vidal, X. Sanjuan, N. Guillen Díaz-Maroto, A. Soriano, J. Guardiola, N. Albert, M. Martínez-Villacampa, I. López, C. Santos, J. Serra-Musach, R. Salazar, G. Capellà, A. Villanueva, D. G. Molleví
Preoperative chemoradiotherapy followed by surgical mesorectal resection is the standard of care for locally advanced rectal carcinomas. Yet, predicting that patients will respond to treatment remains an unmet clinical challenge.
Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma Ann. Oncol. (IF 11.855) Pub Date : 2017-06-14 M. Dreyling, F. Morschhauser, K. Bouabdallah, D. Bron, D. Cunningham, S. E. Assouline, G. Verhoef, K. Linton, C. Thieblemont, U. Vitolo, F. Hiemeyer, M. Giurescu, J. Garcia-Vargas, I. Gorbatchevsky, L. Liu, K. Koechert, C. Peña, M. Neves, B. H. Childs, P. L. Zinzani
Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms.
Consolidative proton therapy after chemotherapy for patients with Hodgkin lymphoma Ann. Oncol. (IF 11.855) Pub Date : 2017-08-09 B. S. Hoppe, C. E. Hill-Kayser, Y. D. Tseng, S. Flampouri, H. M. Elmongy, O. Cahlon, N. P. Mendenhall, A. Maity, L. A. McGee, J. P. Plastaras
We investigated early outcomes for patients receiving chemotherapy followed by consolidative proton therapy (PT) for the treatment of Hodgkin lymphoma (HL).
Early-stage mantle cell lymphoma: a retrospective analysis from the International Lymphoma Radiation Oncology Group (ILROG) Ann. Oncol. (IF 11.855) Pub Date : 2017-06-27 B. S. Dabaja, A. D. Zelenetz, A. K. Ng, R. W. Tsang, S. Qi, P. K. Allen, D. Hodgson, U. Ricardi, R. T. Hoppe, R. Advani, P. M. Mauch, L. S. Constine, L. Specht, Y. Li, S. A. Terezakis, A. Wirth, G. Reinartz, H. T. Eich, B. M. P. Aleman, P. Barr, J. Yahalom
Mantle cell lymphoma (MCL) rarely presents as early-stage disease, but clinical observations suggest that patients who present with early-stage disease may have better outcomes than those with advanced-stage disease.
Reduced-intensity versus reduced-toxicity myeloablative fludarabine/busulfan-based conditioning regimens for allografted non-Hodgkin lymphoma adult patients: a retrospective study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire Ann. Oncol. (IF 11.855) Pub Date : 2017-05-30 A. Le Bourgeois, M. Labopin, D. Blaise, P. Ceballos, S. Vigouroux, R. Peffault de Latour, A. Marçais, C. E. Bulabois, J. O. Bay, S. Chantepie, E. Deconinck, E. Daguindau, N. Contentin, I. Yakoub-Agha, J. Cornillon, M. Mercier, P. Turlure, A. Charbonnier, P. S. Rorhlich, S. N’Guyen, N. Maillard, T. Marchand, M. Mohty, P. Chevallier
Fludarabine/busulfan-based conditioning regimens are widely used to perform allogeneic stem-cell transplantation (allo-SCT) in high-risk non-Hodgkin lymphoma (NHL) patients. The impact of the dose intensity of busulfan on outcomes has not been reported yet.
Beyond first-line non-anthracycline-based chemotherapy for extranodal NK/T-cell lymphoma: clinical outcome and current perspectives on salvage therapy for patients after first relapse and progression of disease Ann. Oncol. (IF 11.855) Pub Date : 2017-07-08 S. H. Lim, J. Y. Hong, S. T. Lim, H. Hong, J. Arnoud, W. Zhao, D. H. Yoon, T. Tang, J. Cho, S. Park, Y. H. Ko, S. J. Kim, C. Suh, T. Lin, W. S. Kim
Current standard treatment, including non-anthracycline-based chemotherapy and optimal combining of radiotherapy, has dramatically improved outcomes of patients with extranodal natural killer/T-cell lymphoma (ENKTL) during the last decade. This study was conducted to investigate the clinical outcome of ENKTL patients with relapsed or progressive disease after initial current standard therapy.
Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II–III trial Ann. Oncol. (IF 11.855) Pub Date : 2017-07-04 M. G. Ghi, A. Paccagnella, D. Ferrari, P. Foa, D. Alterio, C. Codecà, F. Nolè, E. Verri, R. Orecchia, F. Morelli, S. Parisi, C. Mastromauro, C. A. Mione, C. Rossetto, M. Polsinelli, H. Koussis, L. Loreggian, A. Bonetti, F. Campostrini, G. Azzarello, C. D’Ambrosio, F. Bertoni, C. Casanova, E. Emiliani, M. Guaraldi, F. Bunkheila, P. Bidoli, R. M. Niespolo, A. Gava, E. Massa, A. Frattegiani, F. Valduga, G. Pieri, T. Cipani, D. Da Corte, F. Chiappa, E. Rulli
Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3–4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy.
Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study Ann. Oncol. (IF 11.855) Pub Date : 2017-06-23 A. Psyrri, C. Fortpied, G. Koutsodontis, M. Avgeris, C. Kroupis, N. Goutas, J. Menis, L. Herman, L. Giurgea, É. Remenár, M. Degardin, I. S. Pateras, J. A. Langendijk, C. M. L. van Herpen, A. Awada, J. R. Germà-Lluch, H. R. Kienzer, L. Licitra, J. B. Vermorken
EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(−) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered.
TPF plus cetuximab induction chemotherapy followed by biochemoradiation with weekly cetuximab plus weekly cisplatin or carboplatin: a randomized phase II EORTC trial Ann. Oncol. (IF 11.855) Pub Date : 2017-06-16 P. M. Specenier, E. Remenar, J. Buter, D. L. Schrijvers, C. Bergamini, L. F. Licitra, A. Awada, P. M. Clement, C. Fortpied, J. Menis, J. B. Vermorken
Our aim was to test the safety of cetuximab added to chemoradiation with either cisplatin or carboplatin after prior induction chemotherapy.
Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT Ann. Oncol. (IF 11.855) Pub Date : 2017-07-29 M. M. Regan, B. A. Walley, P. A. Francis, G. F. Fleming, I. Láng, H. L. Gómez, M. Colleoni, C. Tondini, G. Pinotti, M. Salim, S. Spazzapan, V. Parmar, T. Ruhstaller, E. A. Abdi, R. D. Gelber, A. S. Coates, A. Goldhirsch, O. Pagani
Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation.
Stromal lymphocyte infiltration after neoadjuvant chemotherapy is associated with aggressive residual disease and lower disease-free survival in HER2-positive breast cancer Ann. Oncol. (IF 11.855) Pub Date : 2017-06-16 A.-S. Hamy, J.-Y. Pierga, A. Sabaila, E. Laas, H. Bonsang-Kitzis, C. Laurent, A. Vincent-Salomon, P. Cottu, F. Lerebours, R. Rouzier, M. Lae, F. Reyal
The role of tumor-infiltrating lymphocytes (TILs) in breast cancer has been extensively studied over the last decade. High TILs levels have been associated with pathological response rate in the neoadjuvant setting and with better outcomes in the adjuvant setting. However, little attention has been paid to changes in TILs and residual TIL levels after neoadjuvant chemotherapy (NAC). We investigated TIL levels before, after chemotherapy, and their dynamics during treatment; and we assessed the correlation of these levels with response to NAC and prognosis.
A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician’s choice in patients with advanced non-small cell lung cancer Ann. Oncol. (IF 11.855) Pub Date : 2017-07-19 N. Katakami, E. Felip, D. R. Spigel, J.-H. Kim, M. Olivo, M. Guo, H. Nokihara, J. C.-H. Yang, N. Iannotti, M. Satouchi, F. Barlesi
Eribulin is a microtubule dynamics inhibitor with a novel mechanism of action. This phase 3 study aimed to compare overall survival (OS) in patients with heavily pretreated non-small cell lung cancer (NSCLC) receiving eribulin to treatment of physician’s choice (TPC).
Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions Ann. Oncol. (IF 11.855) Pub Date : 2017-07-19 C. Mayo-de-las-Casas, N. Jordana-Ariza, M. Garzón-Ibañez, A. Balada-Bel, J. Bertrán-Alamillo, S. Viteri-Ramírez, N. Reguart, M. A. Muñoz-Quintana, P. Lianes-Barragan, C. Camps, E. Jantús, J. Remon-Massip, S. Calabuig, D. Aguiar, M. L. Gil, N. Viñolas, A. K. Santos-Rodríguez, M. Majem, B. García-Peláez, S. Villatoro, A. Pérez-Rosado, J. C. Monasterio, E. Ovalle, M. J. Catalán, R. Campos, D. Morales-Espinosa, A. Martínez-Bueno, M. González-Cao, X. González, I. Moya-Horno, A. E. Sosa, N. Karachaliou, R. Rosell, M. A. Molina-Vila
In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).
The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC Ann. Oncol. (IF 11.855) Pub Date : 2017-06-15 P. N. Aguiar, L. A. Perry, J. Penny-Dimri, H. Babiker, H. Tadokoro, R. A. de Mello, G. L. Lopes
Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection.
Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide Ann. Oncol. (IF 11.855) Pub Date : 2017-06-15 D. E. Rathkopf, M. R. Smith, C. J. Ryan, W. R. Berry, N. D. Shore, G. Liu, C. S. Higano, J. J. Alumkal, R. Hauke, R. F. Tutrone, M. Saleh, E. Chow Maneval, S. Thomas, D. S. Ricci, M. K. Yu, C. J. de Boer, A. Trinh, T. Kheoh, R. Bandekar, H. I. Scher, E. S. Antonarakis
Mutations in the androgen receptor (AR) ligand-binding domain (LBD), such as F877L and T878A, have been associated with resistance to next-generation AR-directed therapies. ARN-509-001 was a phase I/II study that evaluated apalutamide activity in castration-resistant prostate cancer (CRPC). Here, we evaluated the type and frequency of 11 relevant AR-LBD mutations in apalutamide-treated CRPC patients.
Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer Ann. Oncol. (IF 11.855) Pub Date : 2017-06-16 K. Blackwell, P. Gascon, C. M. Jones, A. Nixon, A. Krendyukov, R. Nakov, Y. Li, N. Harbeck
Following the functional and physicochemical characterization of a proposed biosimilar, comparative clinical studies help to confirm biosimilarity by demonstrating similar safety and efficacy to the reference product in a sensitive patient population.
An antisense oligonucleotide targeting TGF-β2 inhibits lung metastasis and induces CD86 expression in tumor-associated macrophages Ann. Oncol. (IF 11.855) Pub Date : 2017-07-24 I. Huber-Ruano, C. Raventós, I. Cuartas, C. Sánchez-Jaro, A. Arias, J. L. Parra, K. Wosikowski, M. Janicot, J. Seoane
The transforming growth factor (TGF)-β pathway is a well-described inducer of immunosuppression and can act as an oncogenic factor in advanced tumors. Several preclinical and clinical studies show that the TGF-β pathway can be considered a promising molecular target for cancer therapy. The human genome has three TGF-β isoforms and not much is known about the oncogenic response to each of the isoforms. Here, we studied the antitumor response to ISTH0047, a recently developed locked nucleic acid-modified antisense oligonucleotide targeting TGF-β2.
Cancer mortality predictions for 2017 in Latin America Ann. Oncol. (IF 11.855) Pub Date : 2017-06-23 G. Carioli, C. La Vecchia, P. Bertuccio, T. Rodriguez, F. Levi, P. Boffetta, E. Negri, M. Malvezzi
From most recent available data, we predicted cancer mortality statistics in selected Latin American countries for the year 2017, with focus on lung cancer.
Oncologist use and perception of large panel next-generation tumor sequencing Ann. Oncol. (IF 11.855) Pub Date : 2017-07-06 A. M. Schram, D. Reales, J. Galle, R. Cambria, R. Durany, D. Feldman, E. Sherman, J. Rosenberg, G. D’Andrea, S. Baxi, Y. Janjigian, W. Tap, M. Dickler, J. Baselga, B. S. Taylor, D. Chakravarty, J. Gao, N. Schultz, D. B. Solit, M. F. Berger, D. M. Hyman
Genomic profiling is increasingly incorporated into oncology research and the clinical care of cancer patients. We sought to determine physician perception and use of enterprise-scale clinical sequencing at our center, including whether testing changed management and the reasoning behind this decision-making.
Development of an integrated electronic platform for patient self-report and management of adverse events during cancer treatment Ann. Oncol. (IF 11.855) Pub Date : 2017-06-23 P. Holch, L. Warrington, L. C. A. Bamforth, A. Keding, L. E. Ziegler, K. Absolom, C. Hector, C. Harley, O. Johnson, G. Hall, C. Morris, G. Velikova
Significant adverse events (AE) during cancer therapy disrupt treatment and escalate to emergency admissions. Approaches to improve the timeliness and accuracy of AE reporting may improve safety and reduce health service costs. Reporting AE via patient reported outcomes (PROs), can improve clinician–patient communication and making data available to clinicians in ‘real-time’ using electronic PROs (ePROs) could potentially transform clinical practice by providing easily accessible records to guide treatment decisions. This manuscript describes the development of eRAPID (electronic patient self-Reporting of Adverse-events: Patient Information and aDvice) is a National Institute for Health Research-funded programme, a system for patients to self-report and manage AE online during and after cancer treatment.
From academia to industry: a road more travelled Ann. Oncol. (IF 11.855) Pub Date : 2017-06-26 W. Pao
In May 2014, I ‘left academia’ to ‘join industry’. Specifically, I left my position as Professor of Medicine, Cancer Biology and Pathology/Immunology/Microbiology; Director, Division of Hematology/Oncology at Vanderbilt University Medical Center; and Director, Personalized Cancer Mecicine at Vanderbilt-Ingram Cancer Center in Nashville, TN, to head up early oncology drug discovery at the Pharma Research and Early Development unit of Roche, based in Basel, Switzerland. In my new role as the Global Head of the Oncology Discovery and Translational Area, I oversee activities spanning from target assessment to phase II clinical trials to leading discovery and clinical scientists, with the goal of developing new medicines for cancer patients. As I pass the three-year mark, I was invited to provide some thoughts about the transition. Note...
Borderline resectable pancreatic cancer: an evolving concept Ann. Oncol. (IF 11.855) Pub Date : 2017-07-19 N. Petrucciani, T. Debs, G. Nigri, F. D’Angelo, J. Gugenheim, G. Ramacciato
We read with interest the article entitled ‘Borderline resectable pancreatic cancer: conceptual evolution and current approach to image-based classification’ published in the Annals of Oncology, in April 2017, by Gilbert et al. . The review extensively discusses the major controversies concerning borderline resectable pancreatic cancer (BRPC): lack of universally agreed definition, variance in institution-by-institution practice, and lack of solid evidence concerning management of these patients. We congratulate the authors for the excellent work and would like to solicit authors’ expert opinion about some points.
Reply to the letter to the editor ‘Borderline resectable pancreatic cancer: an evolving concept’ by Petrucciani et al. Ann. Oncol. (IF 11.855) Pub Date : 2017-05-25 J. W. Gilbert, B. Wolpin, T. Clancy, J. Wang, H. Mamon, A. B. Shinagare, J. Jagannathan, M. Rosenthal
We thank the authors for their generous and thoughtful comments  on our article entitled “Borderline resectable pancreatic cancer: conceptual evolution and current approach to image-based classification,” recently published in Annals of Oncology .
Stromal inflammation, necrosis and HER2 overexpression in ductal carcinoma in situ of the breast: another causality dilemma? Ann. Oncol. (IF 11.855) Pub Date : 2017-07-11 M. Van Bockstal, L. Libbrecht, G. Floris, K. Lambein, S. Pinder
We read with interest the manuscript of Pruneri et al.  concerning tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ (DCIS). TILs were retrospectively studied in an extensive cohort of 1488 patients. DCIS studies are often underpowered due to limited patient numbers, and robust statistical analysis is frequently hampered by low recurrence rates. Therefore, Pruneri et al.  provide truly valuable information for the scientific and oncologic community. However, we do have some remarks regarding the conclusions of this study.
Rituximab for nivolumab plus ipilimumab-induced encephalitis in a small-cell lung cancer patient Ann. Oncol. (IF 11.855) Pub Date : 2017-07-19 M. Ito, S. Fujiwara, D. Fujimoto, R. Mori, H. Yoshimura, A. Hata, N. Kohara, K. Tomii
Immune checkpoint inhibitors (ICIs) have shown antitumor activity against several malignancies. Nivolumab plus ipilimumab has shown promising efficacy in patients with melanoma and small-cell lung cancer (SCLC) [1–4]. ICI-induced encephalitis is an extremely rare immune-related adverse event and little is known about its clinical course and management [1–4]. We report a case of encephalitis induced by nivolumab plus ipilimumab in an SCLC patient, who showed remarkable improvement upon treatment with rituximab.
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