13 December 2017 (Wednesday) - Oncologist Newsletter

The Oncologist” email came today. Maybe not of direct relevance to my daily round, but one or two buts are of passing interest:



The Search for Surrogate Endpoints in Trials in Diffuse Large B-Cell Lymphoma: The Surrogate Endpoints for Aggressive Lymphoma Project

Daniel J. Sargent, Qian Shi, Christopher R. Flowers, Norbert Schmitz, Thomas M. Habermann, Jocelyne Flament, Tommy Fu, Bertrand Coiffier, on behalf of the SEAL group
This commentary describes the progress of the SEAL [Surrogate Endpoints for Aggressive Lymphoma] research group and invites collaboration in sharing data to continue building a large database of individual patient data from multiple clinical trials in DLBCL.

Early Integrated Palliative Care and Reduced Emotional Distress in Cancer Caregivers: Reaching the “Hidden Patients”

Michael Hoerger, Brittany D. Cullen
Caregivers of patients with advanced cancer are affected physically and emotionally by the patient's illness and are too often overlooked by health care systems. This commentary considers recent findings that early integrated palliative care is beneficial for reducing emotional distress in both patients and caregivers.

Development of Molecularly Driven Targeted Combination Strategies

Timothy A. Yap, Jordi Rodon
Targeted therapies are often inadequate when used in isolation as single agents. Combining diverse targeted therapies could optimally impact patient care by overcoming cancer resistance mechanisms. This commentary highlights such combinatorial strategies, including discussion on a recent trial.

Clinical Trials in Pancreatic Cancer: A Long Slog

Thomas Enzler, Susan Bates
Many investigators have turned their efforts toward improving the gemcitabine/nab-paclitaxel combination by the addition of a third agent. This commentary highlights efforts to date, including the Clinical Trial Results by Ko et al.: A Randomized Double-Blinded Phase II Trial of Gemcitabine and Nab-Paclitaxel Plus Apatorsen or Placebo in Patients with Metastati Pancreatic Cancer: The RAINIER Trial.

Clinical Trial Results

A Randomized, Double-Blinded, Phase II Trial of Gemcitabine and Nab-Paclitaxel Plus Apatorsen or Placebo in Patients with Metastatic Pancreatic Cancer: The RAINIER Trial

Andrew H. Ko, Patrick B. Murphy, James D. Peyton, Dianna L. Shipley, Ahmed Al-Hazzouri, Francisco A. Rodriguez, Mark S. Womack, IV, Henry Q. Xiong, David M. Waterhouse, Margaret A. Tempero, Shuangli Guo, Cassie M. Lane, Chris Earwood, Laura M. DeBusk, Johanna C. Bendell

Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Necuparanib Combined with Nab-Paclitaxel and Gemcitabine in Patients with Metastatic Pancreatic Cancer: Phase I Results

Eileen M. O'Reilly, James Roach, Paul Miller, Kenneth H. Yu, Catherine Tjan, Molly Rosano, Silva Krause, William Avery, Julie Wolf, Keith Flaherty, Darrell Nix, David P. Ryan

Breast Cancer

Distinct Effects of Body Mass Index and Waist/Hip Ratio on Risk of Breast Cancer by Joint Estrogen and Progestogen Receptor Status: Results from a Case-Control Study in Northern and Eastern China and Implications for Chemoprevention

Fei Wang, Liyuan Liu, Shude Cui, Fuguo Tian, Zhimin Fan, Cuizhi Geng, Xuchen Cao, Zhenlin Yang, Xiang Wang, Hong Liang, Shu Wang, Hongchuan Jiang, Xuening Duan, Haibo Wang, Guolou Li, Qitang Wang, Jianguo Zhang, Feng Jin, Jinhai Tang, Liang Li, Shiguang Zhu, Wenshu Zuo, Zhongbing Ma, Fei Zhou, Lixiang Yu, Yujuan Xiang, Liang Li, Shuohao Shen, Zhigang Yu
Obesity is a consideration in the pharmacologic intervention for estrogen receptor-positive breast cancer risk. This case-control study among women in Northern and Eastern China was conducted to clarify the possible associations between both general and central obesity and breast cancer risk.

Cancer Diagnostics and Molecular Pathology

ALK Fusions in a Wide Variety of Tumor Types Respond to Anti-ALK Targeted Therapy

Jeffrey S. Ross, Siraj M. Ali, Omotayo Fasan, Jared Block, Sumanta Pal, Julia A. Elvin, Alexa B. Schrock, James Suh, Sahar Nozad, Sungeun Kim, Hwa Jeong Lee, Christine E. Sheehan, David M. Jones, Jo-Anne Vergilio, Shakti Ramkissoon, Eric Severson, Sugganth Daniel, David Fabrizio, Garrett Frampton, Vince A. Miller, Philip J. Stephens, Laurie M. Gay
This article reports a series of 114,200 consecutive clinical cases with comprehensive genomic profiles available to identify ALK fusions that could facilitate the use of precision medicine in both non-small cell lung cancer (NSCLC) and non-NSCLC malignancies.


Carcinoid Syndrome and Costs of Care During the First Year After Diagnosis of Neuroendocrine Tumors Among Elderly Patients

Chan Shen, Yiyi Chu, Daniel M. Halperin, Arvind Dasari, Shouhao Zhou, Ying Xu, James C. Yao, Ya-Chen Tina Shih
Neuroendocrine tumors can secrete hormonal peptides that lead to a condition known as carcinoid syndrome. Patients with carcinoid syndrome bear additional symptom burdens that can be alleviated but not eliminated with the use of somatostatin analogs. This article examines the cost patterns of elderly patients with neuroendocrine tumors during the first year of diagnosis, taking into account the presence of carcinoid syndrome.

Gastrointestinal Cancer

Outcomes of Advanced Gastric Cancer Patients Treated with at Least Three Lines of Systemic Chemotherapy

Valentina Fanotto, Mario Uccello, Irene Pecora, Lorenza Rimassa, Francesco Leone, Gerardo Rosati, Daniele Santini, Riccardo Giampieri, Samantha Di Donato, Gianluca Tomasello, Nicola Silvestris, Filippo Pietrantonio, Francesca Battaglin, Antonio Avallone, Mario Scartozzi, Eufemia Stefania Lutrino, Davide Melisi, Lorenzo Antonuzzo, Antonio Pellegrino, Laura Ferrari, Roberto Bordonaro, Caterina Vivaldi, Lorenzo Gerratana, Silvia Bozzarelli, Roberto Filippi, Domenico Bilancia, Marco Russano, Giuseppe Aprile
This article explores the characteristics of advanced gastric cancer patients receiving a third-line chemotherapy, as well as factors that could be useful in identifying those patients who might benefit from a further line of treatment.

Genitourinary Cancer

Cure in Advanced Renal Cell Cancer: Is It an Achievable Goal?

Dhanusha Sabanathan, John J. Park, Manuel Marquez, Louise Francisco, Natalie Byrne, Howard Gurney
Three case reports of patients with metastatic renal cell cancer, who had a significant response to anti-PD-L1-antibody when used in combination with targeted therapy (bevacizumab), radiotherapy, and anti-CTLA-4 therapy (ipilimumab), are presented. A review of the literature and future scope for combination therapy are discussed.

Lung Cancer

Current Treatments for Surgically Resectable, Limited-Stage, and Extensive-Stage Small Cell Lung Cancer

Thomas E. Stinchcombe
The prevalence of small cell lung cancer has declined in the U.S. as tobacco use has declined; however, current and former smokers are at risk of developing small cell lung cancer. This article focuses on current and emerging treatment options for small cell lung cancer.


Comprehensive Genomic Profiling of 282 Pediatric Low- and High-Grade Gliomas Reveals Genomic Drivers, Tumor Mutational Burden, and Hypermutation Signatures

Adrienne Johnson, Eric Severson, Laurie Gay, Jo-Anne Vergilio, Julia Elvin, James Suh, Sugganth Daniel, Mandy Covert, Garrett M. Frampton, Sigmund Hsu, Glenn J. Lesser, Kimberly Stogner-Underwood, Ryan T. Mott, Sarah Z. Rush, Jennifer J. Stanke, Sonika Dahiya, James Sun, Prasanth Reddy, Zachary R. Chalmers, Rachel Erlich, Yakov Chudnovsky, David Fabrizio, Alexa B. Schrock, Siraj Ali, Vincent Miller, Philip J. Stephens, Jeffrey Ross, John R. Crawford, Shakti H. Ramkissoon
This study highlights the value of comprehensive genomic profiling in the largest known cohort of pediatric glioma patients and explores the most common alterations across diagnosis and anatomic location. Tumor mutational burden and associated genetic factors that may predispose patients to developing a hypermutator phenotype are also discussed.

New Drug Development and Clinical Pharmacology

A Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of Pictilisib in Combination with Erlotinib in Patients with Advanced Solid Tumors

Stephen Leong, Rebecca A. Moss, Daniel W. Bowles, Joseph A. Ware, Jing Zhou, Jill M. Spoerke, Mark R. Lackner, Geetha Shankar, Jennifer L. Schutzman, Ruud van der Noll, Emile E. Voest, Jan H.M. Schellens
This phase I study was designed to investigate the safety and pharmacokinetics of pictilisib in combination with erlotinib in patients with advanced solid tumors.


Feasibility and Efficacy of Microwave Ablation Combined with Iodine-125 Seed Implantation in Local Control of Recurrent Retroperitoneal Liposarcomas: Initial Clinical Experience

Mingjian Lu, Wang Yao, Tao Zhang, Wenzhe Fan, Zhihui Zhong, Jiaping Li, Fujun Zhang
Surgical resection is the primary treatment option for retroperitoneal liposarcomas, but complete resection is difficult and postoperative recurrence and metastasis are common. This prospective study analyzed the feasibility and efficacy of microwave ablation combined with iodine-125 seed implantation in the local control of recurrent retroperitoneal liposarcomas.

Salvage Therapy in Advanced Adult Soft Tissue Sarcoma: A Systematic Review and Meta-Analysis of Randomized Trials

Alessandro Comandone, Fausto Petrelli, Antonella Boglione, Sandro Barni
This systematic review and meta-analysis was performed to assess the efficacy of salvage treatment in pretreated adult type soft tissue sarcomas, gastrointestinal stromal tumors excluded. The objective was to compare the main outcome endpoints (progression-free survival, overall survival, objective response rate) between trials investigating second-line therapy in soft tissue sarcomas to define the importance and the role of subsequent treatment after first-line failure.

Symptom Management and Supportive Care

Effects of Early Integrated Palliative Care on Caregivers of Patients with Lung and Gastrointestinal Cancer: A Randomized Clinical Trial

Areej El-Jawahri, Joseph A. Greer, William F. Pirl, Elyse R. Park, Vicki A. Jackson, Anthony L. Back, Mihir Kamdar, Juliet Jacobsen, Eva H. Chittenden, Simone P. Rinaldi, Emily R. Gallagher, Justin R. Eusebio, Sarah Fishman, Harry VanDusen, Zhigang Li, Alona Muzikansky, Jennifer S. Temel
This article reports a single-center randomized clinical trial that evaluated the effect of early integrated specialty palliative care on patient- and caregiver-reported outcomes in patients with newly-diagnosed, incurable cancers. It was hypothesized that caregivers of patients assigned to early integrated palliative care would report lower psychological distress and better quality of life compared with caregivers of patients assigned to usual oncology care.

Brief Communications

In-Hospital Outcomes of Tumor Lysis Syndrome: A Population-Based Study Using the National Inpatient Sample

Urshila Durani, Nilay D. Shah, Ronald S. Go
Tumor lysis syndrome (TLS) is an oncologic emergency characterized by metabolic abnormalities leading to organ failure. Complications of TLS can lead to delays in chemotherapy or dose reductions, resulting in less effective treatment. The objective of this study was to describe the incidence of TLS in recent years and the associated in-hospital mortality and morbidity using a national discharge database.

Narratives in Oncology

Finding Hope in Uncertain Times

David Kimball
A lung cancer survivor reflects on facing an uncertain future and beating the odds, on lessons learned, on planning, and especially, on hope.

Letters to the Editor

The Issue of Tissue in Molecular Stratification

Min-Han Tan, Yukti Choudhury, Puay Hoon Tan, Quan Sing Ng, Chee Keong Toh, Ravindran Kanesvaran
This letter reflects on the importance of external validation, in real-world settings, for clinical application.

In Reply

Guillermo de Velasco, Aedín C. Culhane, Daniel Y.C. Heng, Sabina Signoretti, Toni K. Choueiri
This letter responds to the letter from Tan et al., noting points of agreement and encouraging efforts to share genomic signatures and codes that will make future research faster and more effective.

ClinVar Is a Critical Resource to Advance Variant Interpretation

Heidi L. Rehm, Steven M. Harrison, Christa L. Martin
In this Letter to the Editor, potentially flawed conclusions of a recent study are discussed.

In Reply

William Gradishar, Krystal Brown, Erin Mundt, Susan Manley
This Letter to the Editor responds to concerns regarding a recently published analysis of BRCA1 and BRCA2 variant classifications between a single testing laboratory (Myriad Genetic Laboratories) and a database of user-submitted variant classifications (ClinVar).

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