tbuckley/cabot-search huggingface dataset:
Resection of isolated metastases to the pancreas: An institutional retrospective review.
Authors: Benjamin Adam Goldenberg, Sharlene Gill
Journal: Journal of Clinical Oncology (2014)

365 Background: Resection of isolated metastases in good performance status patient (pts) has increasingly become an accepted standard of care. While resection of hepatic and pulmonary metastases from selected cancers such as CRC and RCC have supportive evidence, the safety and effectiveness of pancreatic resections for metastases from these same tumour sites is not as well established. We aim to identify the optimal assessment and selection criteria which would best predict a favourable outcome from pancreatic metastatectomy. Methods: A prospective pathology database was used to identify pts who underwent partial or total pancreatectomy for solid tumour metastases to the pancreas between Sept 2000 to May 2013. Demographic, histologic, surgical and survival data was collected and analyzed using descriptive statistics. Results: 19 pts were identified and included. Follow-up time ranged from 5 months to 8 years. Most common primary sites were RCC (42%,) CRC (11%) and GIST (11%). Favourable outcome, defined as an event-free survival greater than 12 mos from pancreatectomy, was observed in 63% (12/19) and was associated with a higher proportion of RCC (50% vs 14%), pancreas as M1 presentation (58% vs 43%), longer time from presentation to resection (median 5mos vs 2mos), multidisciplinary conference (MDC) review (33% vs 14%) and preop PET (42% vs 14%). No differences were observed by age or gender. Median postoperative length of stay was 22.1 days. Conclusions: Resection of pancreatic metastases remains a rare indication. Given the morbidity and extended LOS associated with pancreatectomy, careful patient selection is required. In this small retrospective series, favourable outcomes were more frequently associated with RCC primary, delayed resection, pre-op MDC and PET staging. Multicentre surgical registries would enhance future analysis and better guide patient selection.
Health-related quality of life changes due to high-dose rate brachytherapy, low-dose rate brachytherapy, or intensity-modulated radiation therapy for prostate cancer.
Authors: Tobin Joel Crill Strom, Alex Cruz, Nicholas Figura, Kushagra Shrinath, Kevin Nethers, Eric Albert Mellon, Daniel Celestino Fernandez, Amarjit Saini, Dylan Hunt, Randy Heysek, Richard Wilder
Journal: Journal of Clinical Oncology (2016)

72 Background: To compare urinary, bowel, and sexual health-related quality of life (HRQOL) changes due to high-dose rate (HDR) brachytherapy, low-dose rate (LDR) brachytherapy, or intensity modulated radiation therapy (IMRT) monotherapy for prostate cancer. Methods: Between January 2002 and September 2013, 413 low-risk or favorable intermediate-risk prostate cancer patients were treated with HDR brachytherapy monotherapy to 2,700-2,800 cGy in two fractions (n=85), iodine-125 LDR brachytherapy monotherapy to 14,500 cGy in one fraction (n=249), or IMRT monotherapy to 7,400-8,100 cGy in 37-45 fractions (n=79) without pelvic lymph node irradiation. No androgen deprivation therapy was given. Patients used an International Prostate Symptoms Score questionnaire, an Expanded Prostate cancer Index Composite-26 bowel questionnaire, and a Sexual Health Inventory for Men questionnaire to assess their urinary, bowel, and sexual HRQOL, respectively, pre-treatment and at 1, 3, 6, 9, 12, and 18 months post-treatment. Results: Median follow-up was 32 months. HDR brachytherapy and IMRT patients had significantly less deterioration in their urinary HRQOL than LDR brachytherapy patients at 1 and 3 months post-irradiation. The only significant decrease in bowel HRQOL between the groups was seen 18 months following treatment, at which point IMRT patients had a slight, but significant, deterioration in their bowel HRQOL compared with HDR and LDR brachytherapy patients. HDR brachytherapy patients had worse sexual HRQOL than both LDR brachytherapy and IMRT patients following treatment. Conclusions: IMRT and HDR brachytherapy cause less severe acute worsening of urinary HRQOL than LDR brachytherapy. However, IMRT causes a slight, but significant, worsening of bowel HRQOL compared with HDR and LDR brachytherapy.
A phase II trial of erlotinib in combination with gemcitabine and capecitabine in previously untreated metastatic/recurrent pancreatic cancer
Authors: D. Oh, K. Lee, K. Lee, C. Sohn, D. Zang, H. Ryoo, H. Song, J. Kim, Y. Bang
Journal: Journal of Clinical Oncology (2008)

4638 Background: To confirm the efficacy and toxicity of erlotinib in combination with gemcitabine and capecitabine when used as a first-line therapy in patients with metastatic/recurrent pancreatic cancer based on the result of NCIC PA.3 (erlotinib+gemcitabine) and interim result of UK (gemcitabine+capecitabine). Methods: Patients with advanced pancreatic adenocarcinoma, with at least one measurable lesion were eligible for the study. Other eligibility criteria included: no previous palliative chemotherapy, Karnofsky performance status ≥50, and adequate organ function. Locally advanced pancreatic cancer was excluded. Erlotinib was given at a dose of 100mg daily from day 1 to day 28. Gemcitabine was given intravenously at a dose of 1,000mg/m2 over 30 min on days 1,8,15 and capecitabine was given at a dose of 1,660mg/m2/day from day 1 to day 21, repeated every 4 weeks. Response was assessed according to RECIST every 8 weeks. 4 month-progression-free survival (PFS) was the primary end point. Planned sample size was 44. Results: A total of 36 patients from 8 centers were enrolled between Feb 2007 and Dec 2007. (median age: 58 years, Karnofsky performance status 100/90/80/70/60 (5/14/8/3/1)). Nineteen patients were evaluable for response at the time of interim analysis. Partial responses were achieved in 5 patients, resulting in an response rate of 26% (95% CI, 6.4–45.6%). Twelve patients (63%) had stable disease. Overall disease control rate was 89% and clinical benefit response was 63%. The median response duration was 2.9 months (95% CI, 0.4–5.3 months). The PFS was 6.6 months (95% CI, 3.9–9.3 months) and the overall survival was not reached yet. Four month-PFS was 74%. The major grade 3/4 hematologic toxicities were: neutropenia (6.0%), thrombocytopenia (5.0%), anemia (2.0%). The major grade 3/4 nonhematologic toxicities were: nausea (6.0%), vomiting (6.0%), anorexia (6.0%), rash (3%) and hand-foot syndrome (0%). No treatment-related deaths occurred during the study. Conclusions: Erlotinib in combination with gemcitabine and capecitabine showed promising efficacy and good tolerability in metastatic/recurrent pancreatic cancer. No significant financial relationships to disclose.
Maintenance therapy with the TLR-9 agonist MGN1703 in the phase II IMPACT study of metastatic colorectal cancer patients: A subgroup with improved overall survival.
Authors: Hans-Joachim Schmoll, Jorge Riera-Knorrenschild, Hans-Georg Kopp, Frank Mayer, Hendrik Kroening, Dieter Nitsche, Jan Kuhlmann, Reinhard Ziebermayr, Johannes Andel, Dirk Arnold, Manuel Schmidt, Burghardt Wittig, Werner Scheithauer
Journal: Journal of Clinical Oncology (2015)

680 Background: Patients with mCRC and disease control after induction with first-line chemotherapy +/- bevacizumab were included in the double-blind placebo-controlled phase II IMPACT trial, aiming to assess the clinical efficacy, safety, and immunological effects of the immunomodulator MGN1703, a potent TLR9 agonist, given at the dose of 60 mg subcutaneously twice weekly as switch maintenance after first line induction therapy in mCRC. Methods: The trial was prematurely closed after randomization of 59 patients. The final analysis showed a superior effect of MGN1703 compared to placebo with hazard ratios (HR) for the primary endpoint PFS on maintenance of 0.55 (p=0.041) and 0.56 (p=0.070) by local investigator assessment or independent radiological review, respectively. Exploratory PFS analyses of pretreatment characteristics identified patients with normalized CEA, objective response, and the presence of activated NKT cells at the end of induction chemotherapy to benefit the most from maintenance with MGN1703. We analysed the impact of these factors on the secondary endpoint overall survival (OS). Results: At time of final study analysis, OS data were not mature. Only 35% of MGN1703 patients had an event, as opposed to 50% of placebo patients. The HR for OS of whole study population was 0.63 (median 22.6 vs. 15.1 months, p=NS). The subgroup of patients randomized into the study with confirmed RECIST response had a HR of 0.40 (median 24.5 vs. 15.1 months, p=NS), suggesting this may be the population with greater benefit. HR for patients with normalized CEA or with activated NKT cells were 0.69 and 0.43, respectively. Based on this evidence, in the phase III IMPALA study patients with objective response after standard induction therapy are randomized to standard treatment or switch maintenance with MGN1703. CEA and activated NKT cells are stratification factors for the study and will be prospectively assessed. Conclusions: The pretreatment characteristics predictive of a PFS benefit in the IMPACT study seem to retain their value also in exploratory analyses for OS. This information has been used to design the phase III IMPALA study, currently recruiting patients. Clinical trial information: NCT01208194.
Immunotherapy of advanced melanoma by intratumoral injections of autologous, purified dendritic cells transduced with gene construct of interleukin-12, with dose-dependent expression under the control of an oral activator ligand.
Authors: D. J. Schwartzentruber, J. M. Kirkwood, M. J. Guarino, J. M. Richards, O. Hamid, S. O'Day, J. J. Nemunaitis, J. E. Talmadge, S. Chada, K. B. Menander, K. Shafer-Weaver, J. H. Senesac, M. O. Thornton, J. J. Lewis, R. B. Herberman
Journal: Journal of Clinical Oncology (2011)

2540 Background: RTS-IL12 is a novel synthetic gene construct in an adenovirus vector, with IL-12 expression only turned on when an oral small molecule activator ligand (AL) triggers the promoter of the gene. Syngeneic dendritic cells (DC) transduced with RTS-IL-12 injected intra-tumorally + oral AL induced IL-12 and associated genes only locally, triggering systemic, specific anti-tumor cytotoxic T cells and regression of B16 melanoma and other mouse tumors. A Phase 1 trial was initiated to evaluate safety, mechanism of action (MOA) and clinical activity of DC-RTS-IL12 in patients with advanced melanoma. Methods: Autologous immature DC-RTS-IL-12s (5x107) are injected intra-tumorally, in combination with 14 days of AL (0.6, 20, 60 or 200 mg /day), for ≤ 5 treatment cycles. Safety, MOA (genomic and immunologic) and clinical responses (CT evaluation by RECIST) are being assessed. Results: Among 7 patients treated, partial or complete regression of injected and some uninjected lesions was observed by CT in 2 patients, with 1 patient having RECIST PR of >11 months. These 2 patients had intratumoral changes in IL-12 associated gene expression, and circulating CD8+ and/or CD4+T cells reactive against several melanoma-associated peptides by ELISPOT. Treatment was generally well tolerated and MTD has not yet been reached. Accrual will end early if there are 4 or more responses. Conclusions: This phase I trial in patients with advanced melanoma has confirmed key findings from mouse tumor models: regression of some uninjected as well as injected tumor lesions, and induction of systemic, specific anti-tumor T cell immunity even at dose levels of AL that do not trigger increases in circulating IL-12 or its associated cytokines.
Efficacy of neoadjuvant TPF (nTPF; docetaxel, T; cisplatin, P; 5FU) in nonselected patients (pts) with head and neck cancer and subsequent radiotherapy (RT) combined with chemotherapy (CT) or cetuximab (Cx)
Authors: N. Bonnin, P. Ceruse, T. Bachelot, P. Zrounba, A. Ramade, P. Pommier, V. Favrel, S. Tartas, C. Ferlay, J. Fayette
Journal: Journal of Clinical Oncology (2008)

6074 Background: nTPF, followed by RT or radiochemotherapy (CRT) with weekly carboplatin (N Engl J Med 2007;357: 1695 and 1705) increased overall survival (OS) and organ preservation. We determine toxicity and efficacy of nTPF in unselected pts, then CRT with P or cetuximab (Cx). Methods: We retrospectively reviewed 123 pts with head and neck cancer (5 M+) treated with nTPF (T and P 75 mg/m2, both d1, F 750 mg/m2/d, d1–5) q 3 wks, for 3 or 4 cycles in three institutions in Lyon (France) between May 2005 and August 2007. Surgery was performed for operable patients in case of PD or insufficient response. Results: Median age was 56 years [32–78]. Localizations: oral cavity (9%), oropharynx (27%), hypopharynx (33%) larynx (19%), rhinopharynx (5%) or other (7%). Two pts died after 1st cycle of nTPF, 1 after 2nd and 2 during RT. After the first cycle, despite systematic use of G-CSF, 23% of pts displayed grade 3–4 neutropenia, with 14% of febrile neutropenia; 24% reversible elevation of creatinine, 7% grade 3–4 diarrhoea and 23% required secondary hospitalization. Despite this toxicity, 115 (93%) pts started a second cycle at the same dose. Tolerance of the following cycles was better with only 0.9 to 2.9% of febrile neutropenia and 5% of secondary hospitalization. For response, 112 pts were assessable after nTPF: radiological OR was 96% (29% CR, 67% PR). Twenty six pts had surgery of tumor (16 radical and 10 conservative), and 43 had lymph node dissection. RT was done or planed for 113 pts (but 27 missing data): 15 alone, 33 with P (19 q1w, 14 q3w), 31 with Cx and 7 with other CT. After nTPF, combined RT is toxic with for combined q1w P, q3w P and Cx respectively: 47, 61 and 64% (ns) of grade 3–4 toxicity; 25, 38 and 50% (ns) of temporary arrest of RT; 33, 69 and 28% (p=0.041) of definitive arrest of CT. With a median follow-up of 9.4 months CI95% [8.0 - 11.3], 22 pts progressed and 16 are dead. Conclusions: nTPF is highly toxic in unselected patients but seems promising especially in term of organ preservation. Predictive factors of toxicity are needed. After nTPF, RT with q3w P seems too toxic and new modalities (q1w P or Cx) deserve further investigations. No significant financial relationships to disclose.
Axitinib inhibition of [<sup>18</sup>F] fluorothymidine (FLT) uptake in patients (pts) with colorectal cancer (CRC): Implications for cytotoxic chemotherapy combinations.
Authors: C. Hoh, J. R. Infante, H. A. Burris, J. C. Tarazi, S. Kim, B. Rosbrook, T. R. Reid
Journal: Journal of Clinical Oncology (2011)

3591 Background: Axitinib is an oral, potent, and selective inhibitor of VEGF receptors (VEGFR) 1, 2, and 3. Clinical trials of VEGFR inhibitors in combination with cytotoxic chemotherapies have yet to yield positive results. Inhibition of cancer cell proliferation by VEGFR inhibitors may be antagonizing cytotoxic chemotherapy. This serial FLT-PET imaging study was performed to determine whether continuous dosing of axitinib inhibits FLT uptake and whether a 3- or 7-day drug holiday could reverse the FLT uptake inhibition. Methods: Pts with CRC or other GI cancers with suitable lesions were enrolled. Axitinib 7 mg (cohort 1) or 10 mg (cohort 2) twice daily (BID) starting dose was administered continuously for 7 days, then interrupted for ≥7 days. Dynamic and whole-body FLT-PET/CT scans were obtained at baseline, at the end of 7 days of continuous axitinib BID dosing, and then 3 and 7 days after axitinib interruption. Kinetic parameters calculated included the Patlak influx constant (Kpatlak) and changes in standardized uptake values (SUVmax, SUVmean). For liver lesions, SUVmean was used. Results: A total of 19 pts were enrolled, 3 and 16 into Cohorts 1 and 2, respectively. 15 had CRC and 4 had other GI cancers; 14 were male, and median age was 56 yrs. Serial FLT-PET data were available for 18 pts: 6 with lung, 5 with liver, 3 with lymph node, 2 with abdominal wall, and 2 with pelvic lesions. Following an initial 7 days of continuous axitinib, tumor FLT uptake (mean DSUV) changed by –46.0% (95% CI: –31.8%, –60.2%) from baseline. Then, after 3 days of axitinib holiday, tumor FLT uptake increased from nadir by +54.5% (95% CI: +17.5%, +91.5%), which further increased by +96.6% (95% CI: +36.4%, +156.8%) after 7 days of axitinib holiday. Conclusions: Continuous axitinib therapy for 7 days markedly inhibited fluorothymidine uptake. Since inhibition of cancer cell proliferation can protect against the cytotoxic effects of chemotherapeutics, this could explain the failure of VEGFR inhibitor + chemotherapy regimens to improve chemotherapy. Inclusion of a short drug holiday in axitinib dosing schedule may allow resensitization of cancer cells.
Willingness to pay to prevent chemotherapy-induced nausea and vomiting.
Authors: P. Miller, S. Balu, D. Buchner, M. Walker, E. J. Stepanski, L. S. Schwartzberg
Journal: Journal of Clinical Oncology (2011)

6068 Background: This study assessed willingness to pay (WTP) to avoid chemotherapy induced nausea and vomiting (CINV) among 303 cancer patients. Methods: WTP was assessed using results from a conjoint survey. Patients viewed 25 scenarios each involving 2 descriptions of CINV and indicated which they preferred. Each scenario represented a combination of levels from 8 CINV related attributes. Importance scores assessing attribute contribution to selection and WTP values were calculated using preference coefficients from a series of probit models. Results: Patients were 79% Caucasian and 16% African American. Mean age was 59.4 years (range=26-86). 40% had breast cancer, 35% lung cancer, and 25% colorectal cancer. 68% were on HEC/MEC, 22% had been on HEC/MEC in the last 6 months, and 10% were chemotherapy naïve. Important scores for attributes were cost: 0.21, chance nausea: 0.07, length nausea: 0.15, severity nausea: 0.16, chance vomiting: 0.02, frequency vomiting: 0.07, length vomiting: 0.18, and dehydration: 0.15, indicating cost was the strongest driver of patient choice and choice was driven more by a desire to avoid nausea than vomiting. Patients were willing to pay to avoid > 30% chance of nausea (WTP to avoid 50%: $42.61; WTP to avoid 70%: $49.57), > 1 day of nausea (2-5 days: $62.80; 5+ days: $107.50), vomiting > 1-2 times/day (3-5 times/day: $45.52; 5+ times/day: $52.10), and vomiting longer than a half-day (1 day: $20.12; 2-5 days: $133.05) with p-values from 0.0004 to <.0001. Patients with income $40,000+ were willing to pay more than others to avoid more than 1 day of nausea (2-5 days: difference=$93.23; 5+ days: difference=$107.43) and nausea that impaired self-care ($42.62) with p-values from 0.01 to <0.0001. Breast cancer patients were willing to pay less to avoid a 25% chance of vomiting versus lung (difference=$49.95; p=0.0083) and colorectal cancer patients (difference=$50.80; p=0.0166), respectively. WTP also varied by disease stage, ECOG performance status, HEC/MEC group, and whether patients had worked while on chemotherapy. Conclusions: The study identifies a significant WTP to avoid nausea and vomiting and substantial group differences in WTP that could be incorporated into the management of CINV.
Repeated ambulatory intrapleural chemotherapy for malignant pleural mesothelioma.
Authors: J. Javidfar, J. R. Sonett, M. E. Ginsburg, J. Miller, E. Hare, M. Bacchetta, R. Fawwaz, R. N. Taub
Journal: Journal of Clinical Oncology (2011)

7088 Background: Malignant pleural mesothelioma (MPM) is associated with a poor prognosis and high mortality rate. Multimodal regimens involving extirpative lung or pleural surgery have had limited success and may be ill-suited for many patients. We offer an alternative multimodal lung-sparing treatment regimen for MPM. Methods: This is a single institution review of 25 patients with advanced MPM who underwent thoracoscopic intrapleural (IP) port placement and were treated with repeated, ambulatory IP chemotherapy (cisplatin and doxorubin). Select patients received concurrent IV pemetrexed and cisplatin or carboplatin. After 8 weeks the pleural space was imaged with radioactive technetium-labeled sulfur colloid. If the distribution was uniform, patients were given 15 mCi IP P-32. Following treatment, catheters were removed, and pleural surfaces were inspected and biopsied by video thoracoscopy. Select patients with progressive disease underwent additional surgery. Statistical analysis was done using Stata/IC 11.0 (Stata Corporation, College Station, Texas). Results: Twenty-five adult patients (20 male, median age 70, range 45-80) underwent ambulatory IP chemotherapy. Eight patients had pleural and peritoneal involvement. Few complications were attributed to IP chemotherapy. Median overall survival time was 12 months (interquartile range 7.7-20.1). Thirteen patients received concurrent IV chemotherapy. This subgroup had an improved median survival of 16.3 months (range 1.3-49.5) vs 10.5 months (5.7-31.8) without IV chemotherapy (p=0.83). Seven patients received IP P-32 radiotherapy. This did not appear to affect survival. Nine patients underwent additional surgery (3 extrapleural pneumonectomy and 6 pleurectomy/ decortication); this did not appear to affect survival (p=0.14). Conclusions: A multimodal approach including repeated IP chemotherapy, IV chemotherapy, and IP radiation is a feasible, safe alternative for select patients with advanced MPM, including those with multicavity disease. This regimen did not prevent patients from undergoing subsequent surgical procedures. More patients are needed to better power subgroups for analysis, improve selection criteria, and optimize treatment.
Medicare Part D low-income subsidy and disparities in breast cancer treatment.
Authors: Alana Biggers, Joan Neuner, Elizabeth Smith, John A. Charlson, Liliana Pezzin, Purushottam Laud
Journal: Journal of Clinical Oncology (2014)

2 Background: Breast cancer outcomes are worse among black than white women, but the role of income and out-of-pocket costs (OOPCs) in these disparities is understudied. The Medicare D program provided medication insurance for older women and also included a low-income subsidy (LIS) which eliminated or reduced OOPCs among women with low assets and limited income (based on federal poverty level). We examined differences in adherence to HT by race/ethnicity among a Medicare D population, hypothesizing that LIS might reduce racial disparities in HT adherence. Methods: With data collected from a national sample of women enrolled in Medicare Parts A, B, and D, we identified Medicare Part D enrollees ≥65 years diagnosed with breast cancer who underwent mastectomy or breast conserving surgery in 2006-07 and received either tamoxifen or an AI (anastrozole, letrozole, or exemestane) within one year of surgery. Nonadherence rates (medication possession rate of &gt;0.80) were calculated by race and LIS status for each year after first fill up through December 2011. The association of race with HT adherence was examined in unadjusted Chi-square analyses and in regression models adjusted for age, comorbidity, chemotherapy use, and zip code level- income and education. All models utilized GEE to account for within-patient clustering. Results: Among a sample of 23,299 women (50.6% age 65-74, 40.9% age 75-84), 27.2% received LIS. LIS (but not AI use) varied substantially by race, so that 20.6% of white women and 69.7% of black women received the subsidy. In the first year of therapy, differences in adherence by race were statistically significant, but small (64.2% for white, 63.2% for black and 66.7% for Hispanic). Adherence dropped during years 2-3 of the study, but reductions were much smaller among LIS recipients. Results were confirmed in adjusted models. Conclusions: Enrollment in the Medicare D LIS was high among black and Hispanic breast cancer patients, and disparities in adherence to breast cancer HT among these women were small and remained so over three years. Our study offers important information about the role of medication subsidies and SES in adherence, and suggests their potential to reduce the breast cancer outcomes gap by race.