bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype
Authors: Symmans W. Fraser , Wei Caimiao , Gould Rebekah , Yu Xian , Zhang Ya , Liu Mei , Walls Andrew , Bousamra Alex , Ramineni Maheshwari , Sinn Bruno , Hunt Kelly , Buchholz Thomas A. , Valero Vicente , Buzdar Aman U. , Yang Wei , Brewster Abenaa M. , Moulder Stacy , Pusztai Lajos , Hatzis Christos , Hortobagyi Gabriel N.
Published: February 2017

Purpose

To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)–targeted treatment.

Methods

We conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor–negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test.

Results

Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor–negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort.

Conclusion

RCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated.
Barriers and facilitators of navigator-led advance care planning conversations in older patients with cancer.
Authors: Kvale Elizabeth Ann , Huang Chao-Hui , Niranjan Soumya J , Dionne-Odom J Nicholas , Kenzik Kelly , Bevis Kerri S. , Rocque Gabrielle Betty ,   The Patient Care Connect Group
Published: February 2017

17

Background: National guidelines and most individuals endorse advance care planning (ACP) as essential; however, few individuals engage in such planning. Little is known about the role of lay navigators in supporting ACP. We sought to understand facilitators and barriers of successful implementation of ACP conducted by lay cancer navigators. Methods: Semi-structured interviews were conducted with 26 lay navigators at 11 sites across the Southeast who were engaged in ACP implementation using Respecting Choices©. Interview topics included quality of ACP training, ACP conversation knowledge and comfort, barriers and facilitators, and perceived role in navigating patients with advanced cancer. Audio-recorded interviews were transcribed verbatim; thematic content analysis was conducted using NVivo 10 Software. Transcripts were reviewed for major themes and subthemes generated via line-by-line coding. Inter-rater agreement (2 primary coders) was assessed using Cohen’s Kappa ( = 0.81), indicating high agreement. Results: Navigators completed 672 ACP conversations across sites. Facilitators and barriers emerged across 3 domains: patient, navigator, and system domains. System facilitators included physician engagement and oncology-team consultation support while barriers included lack of time and space, lack of stakeholder support, and cultural suspicion. At the navigator level, established rapport was a necessary facilitator while personal discomfort and timing issues were barriers. At the patient level, prior experience with a family member was a facilitator while barriers included limited health literacy, fears, lack of readiness, and a “battle” mentality. Conclusions: Lay navigators can be trained to facilitate advance care planning conversations with cancer patients. Lay navigators identified several areas where additional training and infrastructure support might facilitate ACP in patients with advanced cancer. Future work should focus on designing and evaluating systems of healthcare delivery to support this activity.
Role of emergent palliative radiation therapy in the care of patients with cancer.
Authors: Singer Lisa , Zhang Michael , Braunstein Steve E. , Fogh Shannon E.
Published: February 2017

201

Background: Radiation therapy (RT) provides an important role in the palliative care of patients with cancer. For patients with metastatic spinal cord compression not amenable to surgery, the value of timely palliative RT is well established; however, the value of the rapid application of RT for other chief complaints is less clear. The importance of palliative care service (PCS) involvement in patients treated with RT is becoming increasingly recognized and rapidly instituted RT could compromise this involvement. The purpose of this study was to assess the efficacy of emergent RT in alleviating symptoms in patients with cancer and to assess the extent of PCS in the management of patients treated with emergent RT. Methods: Patients treated with emergent RT were retrospectively identified through automated search of our institution’s radiation oncology electronic health record (EHR). Emergent RT was defined as treatment with RT in 48 hours or less from the time of simulation and flagged as emergent in the EHR by the radiotherapy team. Patients without a diagnosis of cancer were excluded from the study. For patients meeting inclusion criteria, data was collected regarding the chief complaint, completion of treatment, length of RT, and the primary outcomes of involvement of PCS and symptom relief. Results: From January to July 2015, 22 patients with cancer were treated with emergent RT. Prior to RT, 21 of 22 patients received other medical and/or procedural interventions. Sixty-four percent of patients were treated with 5 or fewer fractions and all but 2 patients completed RT. Symptoms improved in 73% of patients. PCS were involved in the care of 36% of patients. Conclusions: Emergent palliative RT provided symptom relief in the majority of patients; however, this study identified a lack of PCS involvement in the care of patients treated emergently. Study of long-term patient outcomes is needed. Future work should focus on developing clinical workflows that will better integrate involvement of PCS in the treatment of patients with palliative RT administered both emergently and non-emergently.
Patient, family member, and clinician perspectives on advance care planning (ACP) in hematology and hematopoietic stem cell transplantation (HSCT).
Authors: Booker Reanne , Simon Jessica , Raffin Bouchal Shelley ,   Advanced Care Planning CRIO Program
Published: February 2017

7

Background: Studies have found that ACP engagement remains low in patients undergoing HSCT in spite of the high risks of treatment-related morbidity and mortality. Methods: This qualitative study used Thorne’s Interpretive Description methodology. Participants were accrued from hematological malignancy outpatient clinics at a tertiary oncology center and underwent audio-recorded semi-structured interviews. Analysis involved meticulous review of interview transcripts. The constant comparative method was utilized; data collection occurred concurrently with analysis until saturation of themes was achieved. Results: The study involved 6 patients, 5 family members and 8 clinicians (physicians, nurses, social worker). Participants thought that ACP was both acceptable and important yet many had not engaged in ACP. Perceived barriers to ACP included: system-related barriers such as lack of process for ACP, lack of time and/or resources; patient-related factors such as lack of understanding of disease, prognosis and/or expectations of HSCT, lack of patient/family understanding of ACP, a desire to ‘focus on positives’; and disease/treatment-related factors such as unpredictability of the disease and treatment trajectories in hematology and HSCT. Potential facilitators identified by participants included: integrating ACP as part of routine HSCT care, involving the multidisciplinary team in ACP, and introducing ACP early and revisiting frequently. Conclusions: This study revealed various barriers and facilitators related to participation in ACP. We are using the results of this study to inform and tailor interventions on ACP at our center. Introducing ACP as part of standard care in HSCT and providing ongoing facilitation of ACP, including discussion of disease and treatment expectations at the outset, and when complications arise, may assist patients and families in recognizing how ACP fits into their care. Given the inherent unpredictability in this population, we suggest revisiting ACP frequently to optimize patient experience and ensure patients and family members are aware of other treatment options including supportive and palliative care.
Association between weight gain and sarcopenic obesity in patients treated with androgen deprivation therapy.
Authors: Mitsuzuka Koji , Kyan Atsushi , Sato Tomonori , Orikasa Kazuhiko , Namima Takashige , Aoki Hiroshi , Miyazato Minoru , Arai Yoichi ,   Tohoku Evidence-Based Medicine Study Group and Michinoku Urological Cancer Study Group
Published: February 2017

189

Background: Weight gain in response to androgen deprivation therapy (ADT) can be a marker for adverse effects of ADT. However, a concomitant decrease in lean mass in response to ADT may decrease the utility of weight gain in terms of sarcopenia. Therefore, the goal of the present study was to analyze the relationship among weight gain, obesity, and sarcopenia in patients undergoing ADT. Methods: Patients with prostate cancer who were hormone-naïve and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight and results from blood tests of lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat and the psoas muscle before and after 1-year of ADT. ADT was limited to a luteinizing hormone-releasing hormone agonist with or without bicalutamide. Results: CT was performed in 72 patients before and after 1 year of ADT. Median age was 74 years (49-83). Median prostate-specific antigen before ADT was 21.9 ng/ml (0.3-3316). Clinical stage was B (43.1%), C (26.4%), and D (29.2%). Mean increase in weight was 2.7% after 1 year of ADT. Mean increase in the area of subcutaneous and visceral fat was 31.3% and 20.7%, respectively. Mean change in the area of the psoas muscle was -8.4%. When patients were divided into two groups according to weight change during 1 year of ADT (Group A (n = 34): weight gain < 3.0%, Group B (n = 38): weight gain ≥ 3.0%), an increase in subcutaneous and visceral fat was significantly more frequent in Group B, whereas the frequency of a decrease in psoas muscle area was not significantly different between the two groups (Group A: -9.5%, Group B: -7.5%, P = 0.11). Pearson correlation coefficients showed a moderate relationship between weight gain and fat accumulation (r = 0.44-0.52), but little relationship between weight gain and a decrease in psoas muscle area (r = 0.18). Conclusions: Fat accumulation tended to increase in patients who gained weight during ADT, whereas a decrease in psoas muscle area was not related to weight change. Sarcopenia could occur despite weight change during ADT. Clinical trial information: UMIN000018478.
Inducible MyD88/CD40 to allow rimiducid-dependent activation for control of proliferation and survival of chimeric antigen receptor (CAR) T cells targeting prostate stem cell antigen (PSCA).
Authors: Slawin Kevin Mark , Mahendravada Aruna , Shinners Nicholas , Chang Peter , Lu An , Crisostomo Jeannette , Morschl Eva , Shaw Joanne , Saha Sunandan , Spencer David M , Foster Aaron E
Published: February 2017

206

Background: PSCA is a cell surface antigen that is overexpressed in a majority of metastatic prostate, transitional cell and pancreatic carcinomas. We describe a novel T cell costimulation switch, inducible MyD88/CD40 (iMC), activated by a small molecule, rimiducid, to enhance survival, proliferation and anti-tumor activity of CAR-T cells targeting PSCA. Methods: T cells were transduced with a retrovirus encoding tandem rimiducid-binding domains,cloned in-frame with MyD88 and CD40 signaling elements and first generation CARs (CAR.ζ) targeting PSCA (SFG-iMC-2A-PSCA.ζ). iMC activation was assessed with and without rimiducid treatment of T cells. Coactivation via iMC and CAR was tested in coculture assays with or without rimiducid using various PSCA+tumor cells, e.g. Capan-1 and HPAC pancreatic adenocarcinoma. Efficacy of iMC-modified CAR-T cells in vivo was assessed using an NSG mouse tumor model. Results: T cells transduced with iMC-PSCA.ζ produced cytokines (e.g., IFN-γ and IL-6) in response to rimiducid; however, IL-2 was only produced when both iMC and CAR were activated simultaneously by rimiducid and tumor antigen. Treatment of NSG mice bearing large (> 200 mm3) HPAC tumors with a single i.v. dose of 1x107 iMC-PSCA.ζ cells resulted in complete tumor elimination in 10/10 mice including both rimiducid-treated and untreated animals, compared to mice receiving non-transduced T cells (p = 0.0003). Weekly rimiducid administration dramatically increased CAR-T cell numbers, resulting in a 23-fold expansion of iMC-PSCA.ζ-modified T cells in the spleen compared to mice not receiving rimiducid four weeks after infusion (p = 0.02). In a dose-titration study, rimiducid administration was required for tumor control, and led to 565- and 948-fold T cell expansion at the tumor site, respectively, when lower numbers (1.25x106 or 6.25x105, respectively) of iMC-PSCA.ζ-modified T cells were given. Conclusions: GoCAR-T cells targeting PSCA, which contain an inducible MyD88/CD40 activation switch, may be an effective adoptive cell therapy for patients with pancreatic, prostate, bladder, and other cancers that overexpress PSCA.
Imaging response during therapy (tx) with radium-223 (Ra-223) for castrate resistant prostate cancer (CRPC) with bone metastases (BM).
Authors: Keizman Daniel , Peer Avivit , Neumann Avivit , Rosenbaum Eli , Neiman Victoria , Gottfried Maya , Kuchuk Iryna , Sarid David , Gez Eliahu , Mermershtain Wilmosh , Rouvinov Keren
Published: February 2017

282

Background: Ra-223 is an alpha emitter that selectively targets BM. It was shown to improve the survival of patients (pts) with CRPC and BM, and thus is approved as a standard tx for these pts. However, the imaging response during Ra-223 tx is poorly defined. We aimed to describe the imaging response in pts with CRPC and BM treated with Ra-223. Methods: We evaluated the CT and bone scans response among pts with CRPC and BM, who were treated with Ra-223. Tx consisted of an injection administered q 4 weeks up to 6 injections. Scans were done at baseline, after 3 injections, and upon completion of 6 injections. Logistic regression model was used to analyze clinicopathologic factors associated with scans response. Results: 51 pts were included (median age 72). 59% (n = 30) were treated post docetaxel chemotherapy. 47% (n = 24) were treated concomitantly with a systemic standard therapy (e.g enzalutamide or abiraterone). 76% (n = 39) completed the planned 6 injections. A clinical benefit (improvement of skeletal pain and performace status) was noted in 67% (n = 34). 53% (n = 27) had a decrease of alkaline phosphatase. The response of bone metastatic disease (number of lesions) at 3 months was improvement in 22% (n = 11), stable in 53% (n = 27), and progression in 25% (n = 13). 1/13 (8%) pts evaluated at 6 months, had a progression of BM versus the 3 months status. Progression (RECIST ) of extraskeletal sites (lymph nodes, lungs, liver, adrenal) at 3 months was noted in 35% (n = 18). Concurrent systemic standard therapy (e.g enzalutamide or abiraterone) (OR 3.3, p = 0.04), Pre-tx PSADT ≥ 3 months (OR 2.62, p = 0.02) and on treatment stable/decreasing LDH (OR 2.9, p = 0.05) were associated with on treatment stable extraskeletal metastatic disease. Conclusions: Progression of BM during Ra-223 was uncommon. A bone flare may be noted during the first 3 months, and should not be confused with BM progression. Clinician should consider repeating a CT scan at 3 months in pts with short pre-tx PSADT, and LDH increase during tx, to exclude extraskeletal metastatic disease progression.
Genomic alterations in upper tract urothelial carcinoma (UTUC) versus urothelial carcinoma of the bladder (UBC).
Authors: Mullane Stephanie A. , de Velasco Guillermo , Choueiri Toni K. , Kantoff Philip W. , Bellmunt Joaquim
Published: February 2017

431

Background: Defining the landscape of genomic alterations in UTUC as well as identifying the genomic differences from UBC, may provide insights into the treatment of UTUC. Methods: We interrogated our enterprise-wide institutional targeted next generation tumor sequencing data to compare genomic alterations in patients with UTUC (n = 25) with UBC (n = 72), irrespective of tumor stage. We described differences in frequencies of somatic mutations and copy number alterations in 300 relevant cancer-associated genes. Results: UTUC and UBC demonstrated differences in somatic alterations. Genes more commonly found in UTUC included FGFR3 (20% v. 7.5%), STAG2 (16% v. 7.5%), RB1 (24% v. 16%), TSC1 (16% v. 5.4%), EP300 (12% v. 5.4%), IGFIR (20% v. 0%), and Notch1 (24% v. 0%) (see table). Alterations in FGFR3 and TP53 co-existed in only on patient. We did identify two UTUC patients with MSH2 alterations, both of whom had previously been diagnosed with Lynch Syndrome. Conclusions: Biologically relevant differences exist between UTUC and UBC. We observed an enrichment of potentially targetable mutations including TSC1 and FGFR3. Findings in the genomic profile underline the need to consider these two locations as unique entities for future biologically driven trials. [Table: see text]
Actionable targets in patients with cisplatin-resistant advanced germ cell tumors.
Authors: Bagrodia Aditya , Kaffenberger Samuel D. , Lee Byron , Lee William , Cha Eugene K. , Sfakianos John , Gao Sizhi Paul , Zabor Emily Craig , Ostrovnaya Irina , Eng Jana , Berger Michael F. , Bajorin Dean F. , Schultz Nikolaus , Sheinfeld Joel , Bosl George J. , Al-Ahmadie Hikmat , Solit David B. , Feldman Darren R.
Published: February 2017

473

Background: Approximately 30% of patients with advanced germ cell tumor (aGCT) will progress after first-line chemotherapy. Nearly half of these patients will die of progressive GCT. We describe potentially actionable mutations in a cohort of patients with platinum-resistant aGCT through targeted sequencing. Methods: 76 patients with cisplatin-resistant (CR) disease were sequenced using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay that examines 341 cancer-related genes. Patients were categorized as CR if they met any of the following criteria: 1) incomplete response to first-line cisplatin-based chemotherapy; 2) nonteratomatous tumor progression after standard chemotherapy; 3) nonteratomatous GCT identified at postchemo surgery. We grouped all somatic mutations into core signal transduction pathways or canonical cell functions to identify potential precise targets for therapy. Results: The majority of patients had nonseminoma histology (n = 64, 84%). International Germ Cell Cancer Collaborative Group risk was good, intermediate, and poor in 34%, 13%, and 53% of patients. 17 patients died of disease. In total, 51 potentially actionable alterations were identified in 36/76 (47%) patients. In the TP53 pathway, 7 MDM2 amplifications and 4 MYCN amplifications that may sensitize to nutlin-3 inhibitors were identified. Within the receptor tyrosine kinase pathway, 3 KIT mutations, 1 KDR amplification, and 1 MET amplification were seen that may sensitize to tyrosine kinase inhibitors. Eleven KRAS mutations, 3 NRAS mutations, 3 BRAF mutations, and 2 RAC1 mutations were see among the RAS pathway with preclinical data suggesting efficacy towards respective inhibitors. Actionable targets were also among the PI3-K, WNT, and cell cycle pathways. Potential targets with chromatin modifying or tumor suppressor functions were also seen. Conclusions: We describe actionable alterations that may guide treatment selection in a significant proportion of patients with CR aGCT. Targeted sequencing of these patients may allow us to enrich future clinical trials with patients whose tumors harbor alterations in the drug target of interest.
Prognostic value of hemoglobin level increase during axitinib treatment for metastatic renal cell carcinoma.
Authors: Johnson Alison Claire , Matias Margarida , Coquan Elodie , Brachet Pierre-Emmanuel , Dugue Audrey Emmanuelle , Molinier Alicia , Mourey Loic , Boyle Helen Jane , Laguerre Brigitte , Helissey Carole , Escudier Bernard J. , Joly Florence
Published: February 2017

580

Background: Axitinib is used after failure of first line treatment for metastatic renal cell carcinoma (mRCC). A common side effect of axitinib is the increase of hemoglobin level (HbL) during treatment with a suspected correlation with better outcome. We examined whether HbL increase during the first 3 months of axitinib treatment is associated with better prognosis. Methods: Retrospective multicenter analysis including patients with mRCC treated with axitinib for at least 3 months from 2012 to 2014 as part of the French temporary use authorization cohort. Progression-free survival (PFS) was analyzed according to the following factors: gender, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic score at axitinib initiation, polycythemia (HbL above 16.5/18.5 g/dL or hematocrit above 56/60% for women/men), and maximum increase in HbL within the first 3 months of treatment. Results: 97 patients were analyzed (71% men; median age at diagnosis: 54.7 years [22; 80]; IMDC: 23%, 49%, and 27% in the favorable, intermediate, and poor-risk group, respectively). Patients received axitinib for a median of 8 months [3; 30]. Grade 2-3 toxicities were observed in 81% of patients. Objective response rate was 32%. The median PFS and OS were 8.9 [7.4; 9.3] and 22 [19.4; not reached] months, respectively. During the first 3 months, 81 patients (84%) experienced HbL increase with a median increase of +2.3g/dL [-1.1; 7.2] and 40 of them (51%) had an increase above this median. Eight patients (8%) presented polycythemia. In univariate analysis, significantly longer PFS was observed for men (p = 0.02), for patients who had a better IMDC prognostic score (p = 0.004), and for patients who experienced an increase of HbL ≥ 2.3 g/dL (with a median PFS of 11.7 vs. 7.4 months; p = 0.025), but not for patients with polycythemia. In a multivariate analysis, after adjustment for IMDC score (p < 0.0001) and gender (p = 0.029), an increase in HbL ≥ 2.3 g/dL was significantly associated with a longer PFS (HR = 0.57, 95%CI [0.34; 0.95]). Conclusions: HbL increase ≥ 2.3g/dL in the first 3 months of axitinib treatment was associated with longer PFS. These results require validation in a prospective trial setting.
Clinical, pathologic, and genomic profiles of exceptional responders to anti−PD1 therapy in renal cell carcinoma.
Authors: Ball Mark Wayne , Johnson Michael Hiroshi , Gorin Michael A. , Rodriguez Maria , Diaz Luis A. , Haffner Michael , Netto George J. , Drake Charles G. , Allaf Mohamad E.
Published: February 2017

625

Background: Previous studies have correlated response to PD−1 blockade with PD−L1 over−expression, as well as cell−mediated immune transcripts). However, factors associated with long−term, durable response to nivolumab in patients with RCC have not yet been elucidated. To better understand these factors, we conducted a study to characterize the two extremes of response to therapy – exceptional responders who had durable, complete response and patients who had primary refractory disease. Methods: Patients with durable, complete response (“exceptional responders”) (n=4) and primary refractory disease (n=3) were analyzed. Immunohistochemical staining for PD−L1, CD8 and FOXP3, whole−exome sequencing and quantitative RNA expression profiling was performed and correlated with clinical outcomes. Results: Exceptional responders had trends toward greater CD8+ lymphocyte infiltrate (126.7 vs 28.8 lymphocytes/hpf), higher number of somatic mutations (67 vs 35 somatic mutations/genome), and higher number of predicted mutation associated neoantigens than primary refractory patients (44 vs 8). Expression analysis demonstrated acute phase and immune tolerance signatures in primary refractory patients, while exceptional responders had higher expression of T cell and innate immune signatures. Conclusions: Exceptional responders and primary refectory patients have distinct pathologic, genomic and RNA expression profiles. Larger studies are needed to fully elucidate the basis of response to PD−1 blockade in patients with renal cell carcinoma.
The Commission on Cancer Psychosocial Distress Screening Standard: The first year in review.
Authors: Miller Nina S. , McCabe Ryan M. , Knutson Allison
Published: February 2017

198

Background: In response to recommendations from the 2007 Institute of Medicine report, Cancer Care for the Whole Patient, the American College of Surgeons’ Commission on Cancer developed a set of Continuum of Care standards, including a patient-centered standard regarding the delivery of psychosocial distress screening to all cancer patients. According to Cancer Program Standards 2012: Ensuring Patient-Centered Care, the accredited cancer program must implement a process to integrate and monitor on-site psychosocial distress screening and referral for the provision of psychosocial care. Patients experience psychological, social, financial, and behavioral issues that can interfere with their treatment plan and adversely affect outcomes. Screening processes result in the identification of distressed cancer patients and assessment and referral pathways to ensure appropriate psychosocial care provision can be obtained. The standard was established in 2012 with a 2015 implementation period allowing programs time to develop a screening, assessment, and referral process tailored to their patient population. Methods: Programs submit documentation to describe their process for delivery of care through an electronic activity report. Documentation of this standard includes the timing for delivery of the psychosocial distress screening tool; methodology; the specific tools selected with preference to validated and reliable screening tools; and a process for assessment, referral and documentation. This presentation will summarize the program submissions for 2015 and include an analysis of the details of the standard compliance as reported by accredited programs. Results: This analysis will include responses from all Commission on Cancer accredited programs reporting on this standard. The analysis will provide information about the trends in the timing, methods, and tools used by programs implementing a psychosocial distress screening process. Conclusions: This analysis will inform future decisions about standardization of a screening process and the feasibility of pooling data across centers.
Impact of preoperative sarcopenia on recurrecnce in gastric cancer surgery.
Authors: Sato Tsutomu , Aoyama Toru , Maezawa Yukio , Kano Kazuki , Segami Kenki , Nakajima Tetsushi , Ikeda Kosuke , Hayashi Tsutomu , Yamada Takanobu , Oshima Takashi , Rino Yasushi , Masuda Munetaka , Cho Haruhiko , Ogata Takashi , Yoshikawa Takaki
Published: February 2017

120

Background: Our previous study clarified that morbidity was a negative prognostic factor and sarcopenia defined by of the handgrip strength was a risk factor for the morbidity in gastric cancer surgery. Sarcopenia was reportedly a negative prognostic factor in colorectal cancer, hepatocellular carcinoma and malignant melanoma. This study aimed to evaluate impact of preoperative sarcopenia on recurrence-free survival (RFS) in gastric cancer surgery. Methods: Between May 2011 and June 2013, 256 consecutive primary gastric cancer patients who underwent curative surgery were retrospectively examined. Patients who received neoadjuvant chemotherapy or were diagnosed with pathological stage IV were excluded. Preoperative skeletal muscle mass was evaluated by bioelectrical impedance analysis and was expressed as skeletal muscle index or SMI (muscle mass/height2) by adjusting absolute muscle mass with height. Preoperative muscle function was measured by hand grip strength (HGS). Each cutoff value was determined as the gender-specific lowest 20% of the distribution of each measurement. Univariate and multivariate analyses were preformed to identify risk factors for RFS using a Cox proportional hazards model. Results: Median age (range) was 66 years (37-85 years). Male to female ratio was 168:88. Median follow-up period was 33.4 months. Pathological stage was I in 160, II in 48 and III in 48 patients. Univariate analysis showed that age, adjuvant chemotherapy, pT, pN, histological type, tumor size, total gastrectomy, low SMI and low HGS were significant risk factors for RFS. Multi-variate Cox’s proportional hazard analyses demonstrated that pT (HR 2.76, p = 0.0001), pN (HR 1.375, p = 0.037), histological type (HR 3.46, p = 0.014), low SMI (HR2.17, p = 0.036) were the significant risk factors for RFS. The three-year RFS was 89.1% in the patients with high SMI and 73.2% in those with low SMI (p = 0.007). Conclusions: Low SMI was an independent risk factor for RFS in Stage I-III gastric cancer. Low HGS, a risk factor for morbidity shown in our previous study, was not a risk independent factor for RFS. Preoperative sarcopenia as the short- and long-term outcomes has a value to be tested in the future prospective studies in gastric cancer surgery.
Efficacy and feasibility of neoadjuvant chemotherapy and chemoradiotherapy for elderly patients with stage IB/II/III (excluding T4) esophageal cancer: Retrospective study.
Authors: Miyamoto Takahiro , Kii Takayuki , Gotoh Masahiro , Asaishi Ken , Terazawa Tetsuji , Shimamoto Fukutaro , Kuwakado Shin , Nishitani Hitoshi , Kawai Masaru , Higuchi Kazuhide ,   OMC
Published: February 2017

135

Background: Neoadjuvant chemotherapy (NAC) of 5-fluorouracil plus cisplatin infusion (FP) is standard therapy for stage IB/II/III (excluding T4) esophageal cancer from results of JCOG9907 and definitive chemoradiotherapy (dCRT) of FP is one of the curative options for resectable esophageal cancer with organ preservation results of JCOG9906 in Japan. However, the efficacy and feasibility of NAC FP and CRT for elderly patients (pts) are unclear. Methods: We examined stage IB/II/III (excluding T4) esophageal cancer pts aged 70 or over, who received NAC FP or dCRT at our institution between April 2008 and August 2015, retrospectively. Results: 16 pts received NAC FP at least 1 course, while 5 pts received dCRT because of intolerability for surgery, reject of surgery, and patient's wish. Median age was 73/75 (NAC FP/dCRT) and pts in NAC FP had more advanced stage cancer compared with pts in dCRT (p = 0.02). With respect to the toxicity, bone marrow depression developed in dCRT with more high frequency compared with NAC FP, but no pts had febrile neutropenia. Adverse effects of fatigue, nausea and appetite loss developed in both group frequently. 3 pts were not performed surgery because of decreased respiratory function, decreased PS and progression disease and 4 pts did not achieved 4 cycle of FP infusion because of leukopenia, decreased renal function, and gastrointestinal toxicity. 12 pts in NAC FP undergone R0 resection surgery and 4 pts had a complete remission. The 5-year progression free survival rate was 50% (95% CI: 12-86%) in dCRT and 50% (95% CI: 20-80%) in NAC FP (p = 0.69). The 5-year overall survival rate was 50% (95% CI: 12-86%) in dCRT and 67% (95% CI: 36-88%) in NAC FP (p = 0.83). Conclusions: NAC FP and dCRT for stage IB/II/III (excluding T4) esophageal cancer might be effective even in pts ≥ 70 years of age. The therapy of dCRT might be one of options for elderly inoperative patients.
PET-CT compared to no PET-CT in the management of potentially resectable colorectal cancer liver metastases: The costs implications of a randomized controlled trial.
Authors: Serrano Aybar Pablo Emilio , Gafni Amiram , Gu Chu-Shu , Julian Jim A. , Moulton Carol-anne , Gallinger Steven , Levine Mark Norman
Published: February 2017

296

Background: PETCAM was a randomized trial evaluating the effect of PET-CT compared to conventional imaging (control) on the surgical management of patients with resectable colorectal cancer liver metastases (CRLM). It concluded that PET-CT did not result in frequent change in surgical management (8·0%, 21/263) with only 2·7% (7/263) avoidance of liver resections. In this study we conducted a cost analysis of these two arms up to one year following randomization. Methods: Health care utilization was collected for all study participants. Unit costs for hospitalization, physician services, chemotherapy and outpatient radiological and endoscopic procedures were obtained from administrative databases. Cost analysis was undertaken from the perspective of a third-party payer (i.e., Ministry of Health). Mean cost with its 95% credible interval was estimated using a Bayesian approach. Results: The estimated mean cost per patient in the PET-CT arm was CAN $45,454 (min-max: 1,340-181,420) and in the control arm, CAN $40,859 (min-max: 279-293,558), with a net difference of CAN $4,327, 95% credible interval -2,207 to 10,614. The primary cost driver was cost of hospitalization for liver surgery (+ $2,997 CAN for the PET-CT arm), mainly due to a longer length of hospital stay for the PET-CT arm compared to control (median 7 days vs. 6 days, P= 0·034) and a higher rate of postoperative complications (52/255, 20% vs. 13/128, 10%, P = 0·014). Baseline characteristics were similar between groups, including a similar number of liver segments involved with cancer, number of segments resected and type of liver resection performed. Conclusions: PET-CT does not appear to provide a significant clinical benefit in the surgical management of patients with resectable CRLM and it is not cost saving compared to control.
Safety and activity of nivolumab monotherapy in advanced and metastatic (A/M) gastric or gastroesophageal junction cancer (GC/GEC): Results from the CheckMate-032 study.
Authors: Le Dung T. , Bendell Johanna C. , Calvo Emiliano , Kim Joseph W. , Ascierto Paolo Antonio , Sharma Padmanee , Ott Patrick Alexander , Bono Petri , Jaeger Dirk , Evans T.R. Jeffry , De Braud Filippo G. , Chau Ian , Christensen Olaf , Harbison Christopher , Lin Chen-Sheng , Janjigian Yelena Yuriy
Published: February 2017

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Background: Patients (pts) with GC/GEC often present with A/M disease, which has a poor prognosis, with 1-year survival < 30%, and few treatment options. Nivolumab is a fully human anti-PD-1 IgG4 monoclonal antibody with a favorable safety profile and efficacy in melanoma, non–small-cell lung cancer, and renal cell carcinoma. The phase I/II, open-label CheckMate-032 study evaluated nivolumab ± ipilimumab in pts with solid tumors. Here, we report initial results for pts with GEC/GC receiving nivolumab monotherapy. Methods: Pts with A/M histologically confirmed GC/GEC, irrespective of PD-L1 status, were assigned to receive nivolumab alone (3 mg/kg IV Q2W) and treated until disease progression (PD) or intolerable toxicity. The primary endpoint was objective response rate (ORR); other endpoints included safety, progression-free survival, overall survival (OS), and biomarker status. Results: 59 pts were enrolled and treated with single-agent nivolumab. Median age was 60 y (range 29–80), and 83% of pts received ≥ 2 prior regimens. At database lock, 10 pts were on active treatment; 49 pts discontinued (PD, n = 40; unrelated adverse events, n = 4; treatment-related adverse events [TRAEs], n = 2; other, n = 3). Pts received a median of 4 doses (range 1–25). ORR was 12% (n = 7/58; 1 complete response, 6 partial responses); 12 pts (21%) had stable disease. Among responders, median duration of response was 7.1 mo (95% CI, 3.0–13.2). Median OS was 6.8 mo (95% CI, 3.3–12.4); 12-mo OS rate was 38% (95% CI, 23.2–52.7). 39% of tumor samples were PD-L1 positive ( ≥ 1% cutoff). ORRs in pts with PD-L1-positive and -negative tumors were 18% and 12%, respectively. TRAEs occurred in 66% of pts; most were Grade 1/2. Grade 3/4 TRAEs occurred in 14% of pts and included pneumonitis, fatigue, diarrhea, vomiting, hypothyroidism, and increased aspartate and alanine aminotransferase and alkaline phosphatase levels. No treatment-related deaths occurred. Conclusions: Nivolumab monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated pts with GC/GEC. Objective responses occurred in pts with PD-L1-positive and -negative tumors. Clinical trial information: NCT01928394.
A single institute retrospective trial of concurrent chemotherapy with SIR-Sphere versus SIR-Sphere alone in patients with chemotherapy-resistant colorectal cancer liver metastases.
Authors: Cho May Thet , Kessler Jonathan , Park John , Singh Gagandeep , Chen Yi-Jen , Ituarte Philip HG , Fakih Marwan
Published: February 2017

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Background: The use of selective internal radiation therapy (SIRT) with SIR-Spheres in chemotherapy-resistant colorectal cancer liver metastases (CRC-L) has been associated with favorable progression free survival (PFS) and overall survival (OS) when given alone or concurrently with chemotherapy. However, no prospective studies exist for concurrent SIRT and chemotherapy (SIRT-CT) vs. SIRT alone. We conducted a single institute retrospective trial to compare the effect of SIRT-CT to SIRT alone on liver PFS in patients with CRC-L. Methods: Patients (pts) with CRC-L treated with SIR-Spheres at City of Hope between 2009 and 2014 were identified. CRL-L patients treated with SIRT-CT or with SIRT were excluded if they received, following radioembolization, any chemotherapy/targeted regimen on which they did not previously progress. This strategy was adopted to minimize the impact of post-SIRT systemic therapy bias on SIRT-CT/SIRT liver PFS outcome. Pts characteristics included demographics, liver involvement pattern, and lines of prior chemotherapy. Liver PFS, response rate, and toxicities were compared between SIRT-CT and SIRT arms. Kaplan-Meier estimation was used for PFS analysis. Results: 48 CRC-L pts were treated with SIR-spheres; 27 satisfied the post-SIR-spheres systemic treatment criteria (14 SIRT-CT, 13 SIRT) and were included on this study. Pts characteristics included: age (median = 62; range 52-80), sex (18 males), primary site (colon: 23), hepatic disease burden (23 bilobar), 5-FU resistance/intolerance (25/2), and extrahepatic disease (22). Pts characteristics were similar between treatment arms, except for median prior therapies (SIRT-CT = 3, SIRT = 2). No SIRT-CT or SIRT associated ≥ grade 3 toxicities were noted. Disease control rates were 84% (2/13 PR; 9/13 SD) and 14% (2/14 SD on the SIRT-CT and SIRT arms, respectively (p = 0.001). Median PFS in the liver was 176 days in the SIRT-CT group vs. 91 days in the SIRT group (p = 0.0006). Conclusions: In patients with 5-FU refractory CRC-L, SIRT-CT is associated with an increased disease control rate and a prolonged DFS in comparison with SIRT alone.
Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study
Authors: Nogova Lucia , Sequist Lecia V. , Perez Garcia Jose Manuel , Andre Fabrice , Delord Jean-Pierre , Hidalgo Manuel , Schellens Jan H.M. , Cassier Philippe A. , Camidge D. Ross , Schuler Martin , Vaishampayan Ulka , Burris Howard A. , Tian G. Gary , Campone Mario , Wainberg Zev A. , Lim Wan-Teck , LoRusso Patricia , Shapiro Geoffrey I. , Parker Katie , Chen Xueying , Choudhury Somesh , Ringeisen Francois , Graus-Porta Diana , Porter Dale , Isaacs Randi , Buettner Reinhard , Wolf Jürgen
Published: February 2017

Purpose

This two-part, first-in-human study was initiated in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors (FGFRs) to determine the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), and the schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of oral BGJ398, a selective FGFR1-3 tyrosine kinase inhibitor.

Patients and Methods

Adult patients were treated with escalating dosages of BGJ398 5 to 150 mg once daily or 50 mg twice daily continuously in 28-day cycles. During expansion at the MTD, patients with FGFR1-amplified squamous cell non–small-cell lung cancer (sqNSCLC; arm 1) or other solid tumors with FGFR genetic alterations (mutations/amplifications/fusions) received BGJ398 daily on a continuous schedule (arm 2), or on a 3-weeks-on/1-week-off schedule (arm 3).

Results

Data in 132 patients from the escalation and expansion arms are reported (May 15, 2015, cutoff). The MTD, 125 mg daily, was determined on the basis of dose-limiting toxicities in four patients (100 mg, grade 3 aminotransferase elevations [n = 1]; 125 mg, hyperphosphatemia [n = 1]; 150 mg, grade 1 corneal toxicity [n = 1] and grade 3 aminotransferase elevations [n = 1]). Common adverse events in patients treated at the MTD (n = 57) included hyperphosphatemia (82.5%), constipation (50.9%), decreased appetite (45.6%), and stomatitis (45.6%). A similar safety profile was observed using the 3-weeks-on/1-week-off schedule (RP2D). However, adverse event–related dose adjustments/interruptions were less frequent with the 3-weeks-on/1-week-off (50.0%) versus the continuous (73.7%) schedule. Antitumor activity (seven partial responses [six confirmed]) was demonstrated with BGJ398 doses ≥ 100 mg in patients with FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancer.

Conclusion

BGJ398 at the MTD/RP2D had a tolerable and manageable safety profile and showed antitumor activity in several tumor types, including FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancers.
Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2–Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study
Authors: Perez Edith A. , Barrios Carlos , Eiermann Wolfgang , Toi Masakazu , Im Young-Hyuck , Conte Pierfranco , Martin Miguel , Pienkowski Tadeusz , Pivot Xavier , Burris Howard A. , Petersen Jennifer A. , Stanzel Sven , Strasak Alexander , Patre Monika , Ellis Paul
Published: February 2017

Purpose

Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) –targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody–drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study.

Methods

In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review.

Results

T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms.

Conclusion

T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast cancer.
Biases in Recommendations for and Acceptance of Prostate Biopsy Significantly Affect Assessment of Prostate Cancer Risk Factors: Results From Two Large Randomized Clinical Trials
Authors: Tangen Catherine M. , Goodman Phyllis J. , Till Cathee , Schenk Jeannette M. , Lucia M. Scott , Thompson Ian M.
Published: February 2017

Purpose

To identify factors related to who undergoes a prostate biopsy in a screened population and to estimate the impact of biopsy verification on risk factor–prostate cancer associations.

Patients and Methods

Men who were screened regularly from the placebo arms of two large prostate cancer prevention trials (Prostate Cancer Prevention Trial [PCPT] and Selenium and Vitamin E Cancer Prevention Trial [SELECT]) were examined to define incident prostate cancer cohorts. Because PCPT had an end-of-study biopsy, prostate cancer cases were categorized by a preceding prostate-specific antigen/digital rectal examination prompt (yes/no) and noncases by biopsy-proven negative status (yes v no). We estimated the association of risk factors (age, ethnicity, family history, body mass index, medication use) with prostate cancer and quantified differences in risk associations across cohorts.

Results

Men 60 to 69 years of age, those with benign prostatic hyperplasia, and those with a family history of prostate cancer were more likely, and those with a higher body mass index (≥ 25), diabetes, or a smoking history were less likely, to undergo biopsy, adjusting for age and longitudinal prostate-specific antigen and digital rectal examination. Medication use, education, and marital status also influenced who underwent biopsy. Some risk factor estimates for prostate cancer varied substantially across cohorts. Black ( v other ethnicities) had odds ratios (ORs) that varied from 1.20 for SELECT (community screening standards, epidemiologic-like cohort) to 1.83 for PCPT (end-of-study biopsy supplemented with imputed end points). Statin use in SELECT provided an OR of 0.65 and statin use in in PCPT provided an OR of 0.99, a relative difference of 34%.

Conclusion

Among screened men enrolled in prostate cancer prevention trials, differences in risk factor estimates for prostate cancer likely underestimate the magnitude of bias found in other cohorts with varying screening and biopsy recommendations and acceptance. Risk factors for prostate cancer derived from epidemiologic studies not only may be erroneous but may lead to misdirected research efforts.