tbuckley/cabot-search huggingface dataset:
Preoperative or postoperative therapy for resectable gallbladder cancer? A retrospective analysis of patients treated at a single institution.
Authors: V. Siripurapu, J. C. Watson, Y. S. Chun, A. Gumbs, J. P. Hoffman
Journal: Journal of Clinical Oncology (2011)

309 Background: Gallbladder cancer (GBC) is the most common malignancy of the biliary tract. Less than 30% present at an early stage where surgical resection is curative. We examine a cohort of patients with GBC toward determining if preoperative and postoperative treatment of locally advanced GBC demonstrate any differing results in complications or survival. Methods: A retrospective review of patients seen at FCCC with GBC from Jan 1991 to Nov 2008 was performed. Demographics, clinical stage, surgical procedure, AJCC 7th stage, details of neoadjuvant and adjuvant treatment and complications of surgery were analyzed. Results: Fifty-one patients with GBC were identified. Of these, 66% had their GBC found incidentally, 77% had stage 2 or greater cancers, and 35 patients needed liver resection with portal lymphadenectomy. 13 patients had an extrahepatic bile duct resection. 10 patients had extended resections including pancreatoduodenectomy (5) or colectomy (5), while 6 had cholecystectomy alone. 25% (n=13) of the population had preoperative chemoradiation only, 30 % (n=15) had postoperative chemoradiation only, while 15% (n=8) received maintenance chemotherapy only. 10% (n=5) had preoperative and postoperative therapy, while twenty percent of the group (n=10) had surgery only. 49% had recurrences (n=25), with 48% percent of these being local-regional. Median survival was 30 months for the whole group, with 54.6 month median survival for the 41 patients without extended resection. No significant difference in survival was seen comparing preoperative therapy versus postoperative treatment (p=0.13). Five-year survival is 47% for those with minor hepatic resection compared to 25% for those with combined hepatic and colon or pancreatic resection. Conclusions: We present a retrospective view of patients treated in our center, the majority of whom received either preoperative or postoperative adjuvant therapy, both of which had good median survival and acceptable morbidity and mortality. Given the poor survival and high recurrence rate for stage II and greater cancers, we suggest that preoperative or postoperative adjuvant therapy for these cases may be equally effective. No significant financial relationships to disclose.
Cancer screening practices (CSP) among women at risk of hereditary breast and ovarian cancer syndrome (HBOS) before genetic testing in Spain
Authors: C. Saura, D. Fortuny, T. Ramon y Cajal, A. Torres, B. Graña, E. Darder, J. Sanz, J. Brunet, J. Baselga, J. Balmaña
Journal: Journal of Clinical Oncology (2008)

1538 Background: Women at risk of HBOS are recommended biannual/annual clinical breast examination (CBE), annual mammography (MX) and annual pelvic or transvaginal ultrasound (PTVUS) starting at age 25–30y or 5–10y earlier than the youngest case in the family. Compliance with these recommendations before genetic testing is unknown. Methods: Healthy women or with early breast (BC) or ovarian cancer (OC) at risk of HBOS referred to high-risk clinics for BRCA genetic testing were asked to fulfill a self-completed questionnaire about adherence to CBE, MX, and PTVUS before genetic testing. Demographic, clinical or psychological variables were analyzed with chi-square or Fisher exact test with SPSS program. Results: Overall, 214 women completed the questionnaires and were included in the analysis. Median age was 43y (range 19–88), 66% had a previous history of cancer, 53% had a strong family history of HBOS, 31% reported a deleterious mutation in BRCA previously identified in the family, 42% had the perception of being a mutation carrier and 36% had a high risk perception of cancer. Overall, the adherence to CSP was 62% for CBE, 57% for MX and 44% for PTVUS. Within age groups, adherence to CBE was 39% between 19–30y (G1), 58% between 31–50y (G2) and 82% for women >51y (G3), p<0.05; adherence to MX was 33% in G1, 72% in G2 and 69% in G3, p=0.06; adherence to PTVUS was 67% in G1, 68% in G2 and 69% in G3, p=NS. Adherence to MX for women with previous BC or OC was 71% and 25%, respectively, and 89% for women with a previous premalignant breast lesion. No statistically significant differences in adherence to any CSP were identified when adjusted by other potential confounders. Sixty-three percent of women not performing annual MX revealed that the main reason was because their physician did not recommend it. Conclusions: Adherence to specific CSP in women at risk of HBOS before genetic testing is insufficient. Medical awareness about hereditary cancer syndromes may contribute to improve the adherence to CSP in this high-risk population. No significant financial relationships to disclose.
Evaluation of spiritual needs assessments in oncology palliative care: Results of an improvement project.
Authors: Sarah Thirlwell, Valerie Storms, Mareda Kennedy, Diane G. Portman
Journal: Journal of Clinical Oncology (2015)

161 Background: Addressing all facets of serious illness requires attention to patients’ spiritual concerns. At our Cancer Center, we sought to ensure that palliative care (PC) inpatients received evidence-based spiritual care. Methods: Chaplaincy Care, Supportive Care Medicine, and Quality and Safety Departments partnered to improve spiritual care using an iterative Plan-Do-Check-Act Cycle approach. Evidence-based spiritual practices were defined in accordance with the Association of Professional Chaplains and Clinical Practice Guidelines for Quality PC of the National Consensus Project. As a member of the Global Palliative Care Quality Alliance, we also used the web-based Quality Data Collection Tool (QDACT) to guide spiritual assessment. Electronic health record templates were revised to support complete and timely documentation. We monitored performance based on National Quality Forum Measure #1647 for discussion of spiritual/religious concerns. Performance was reviewed monthly by Leadership and with the Chaplaincy Staff. Opportunities to improve performance were discussed and adjustments in practice were made. Results: A total of 1609 oncology patients (average of 89/month) were seen by the inpatient PC team from November 2013–April 2015. With transparent performance reporting and resolution of barriers to spiritual assessment, an increase from 36 to 96% was noted for the percentage of patients with documented spiritual or religious concerns. Spiritual assessment using QDACT indicated that most patients report high spiritual well-being, spiritual peace, and a religious affiliation. Conclusions: As the result of our efforts, the majority of PC oncology patients at our center now have assessment and documentation of spiritual and religious concerns. A team-based approach to quality improvement successfully fostered the integration of spiritual care into oncology palliative care. [Table: see text]
Factors contributing to cure in T2 pancreatic cancer.
Authors: S. Maetani, R. Doi, M. Imamura
Journal: Journal of Clinical Oncology (2011)

234 Background: It is crucial to determine whether cancer therapy achieves cure or merely prolongs time to death from cancer (failure time). Unfortunately, conventional survival tests such as log-rank test and Cox regression fail to distinguish between cure and prolonged failure time, both making a great difference in survival benefit. In 1994, Gamel extended the Boag model to three regressions, allowing us to study whether prognostic factors have significant effect on cure rate or failure time. Using the Gamel-Boag regressions, we study curative effects of clinicopathological factors in pancreatic cancer. Methods: Follow-up data from 452 patients who underwent pancreatectomy for T2 ductal cell cancer were analyzed. The prognostic factors to be studied were converted to binary variables, which include sex, age (&lt;=60 or &gt;60 years), tumor size (&lt;=2 or &gt;2 cm) lymphnode metastasis, and six types of invasions, i.e., serosal, retroperitoneal, portal vain, common bile duct and duodenal invasions. By calculating coefficients of the three regressions and their confidence intervals, we evaluated whether each (or combinations) of these variables are associated with increased cure rate or prolonged failure time. Results: Tthere were 11 relapse-free 5-year survivors. Except for tumor size (TS) and lymphnode metastasis (N), no factors were significantly associated with increased cure rate or prolonged failure time. The only factor found to significantly affect cure was TS; the estimated cure rate being 44% for patients with TS &lt;= 2 cm and 4% otherwise (p=0.0001). This effect was not influenced by N and other factors. Only N significantly accelerated failure time; the median failure time being 11.9 months when N was negative and 6.7 months otherwise (p&lt;0.0001). Thus, both TS and N affected the prognosis significantly but in different ways. By contrast the Cox regression showed that both TS and N were significantly associated with hazard reduction (p=0.003 and p&lt;0.001, respectively), which, however, did no reveal a qualitative difference in survival outcome between TS and N. Conclusions: In T2 pancreatic cancer, a highly significant increase in cure rate is found when TS≤2 cm. This increase is not affected by N or tumor extension to nonpancreatic tissues. No significant financial relationships to disclose.
Surgical resectability after neo-adjuvant FOLFIRINOX for borderline or locally advanced pancreatic adenocarcinoma.
Authors: Mathias Alline, Pierre Emmanuel Colombo, François Quenet, Marta Jarlier, Fabienne Portales, Carmen Llacer, Jean Michel Fabre, Marc Ychou, Philippe Rouanet
Journal: Journal of Clinical Oncology (2015)

421 Background: FOLFIRINOX has already demonstrated its efficiency in metastatic pancreatic cancer (PC). This combination need to be assessed in a neoadjuvant situation for locally advanced non metastatic PC. Methods: From 2009 to 2013, 31 patients with borderline or locally advanced PC received a neoadjuvant treatment with FOLFIRINOX so as to get them to a resectable situation. According to the tumoral response, chemoradiotherapy with gemcitabine was done. The primary analysis endpoint was the resecability rate. Pathologic response, chemotherapy’s toxicity and surgical morbidity were also evaluated. Results: Among the 31 PC, 17 were borderline resectable and 14 locally advanced according to NCCN classification. 16 (52%) received complete chemotherapy with a median of 4 cycles. Toxicity lead to treatment modification or interruption for 9 patients (29%). Grade 3-4 toxicity occurred in 7 patients (24%). 22 patients (71%) underwent chemoradiotherapy after FOLFIRINOX chemotherapy. 13 patients (42%) had disease progression under treatment whereas 18 patients with objective radiologic response or at least stable disease were surgically explored with a resection completed in 13 cases (42%). Surgical morbidity was controlled with grade 1-2 complications for 9 patients (69%) and no mortality. 11 patients (35%) demonstrated a significant pathologic response. Resected patients had a global survival median of 36 months. Conclusions: FOLFIRINOX in a neoadjuvant setting seems feasible with limited morbidity in locally advanced PC with encouraging resecability and pathologic response rates. Resected patients’ survival is promising but need to be confirmed in larger series.
Impact of first-line bevacizumab therapy on the efficacy of subsequent anti-epidermal growth factor antibodies (anti-EGFR) in metastatic colorectal cancer (mCRC).
Authors: Matthew E. Burge, Hui-Li Wong, Belinda Lee, Jeanne Tie, Suzanne Kosminder, Kathryn Maree Field, Ben Tran, Jayesh Desai, Sumitra Ananda, Peter Gibbs
Journal: Journal of Clinical Oncology (2016)

685 Background: The FIRE3 study reported that cetuximab added to first line combination chemotherapy versus the addition of bevacizumab to the same chemotherapy backbone, with a planned switch to the alternative biologic in second line therapy, resulted in improved overall survival. One possible explanation is that the sequence of biologic administration in mCRC impacts on treatment benefit. Examination of the efficacy of anti-EGFR therapy in cohorts where patients have and have not received prior bevacizumab will inform this. Methods: We interrogated our prospective database (ACCORD), which records comprehensive detail on demographics, treatments received and patient outcomes for consecutive mCRC patients in real world practice across multiple institutions in Australia. We included patients receiving 2 nd and subsequent line anti-EGFR monotherapy. Disease control rate (DCR) (partial response plus stable disease), progression free survival (PFS) and overall survival (OS) from the start of anti-EGFR were determined as a function of prior bevacizumab use. Results: From a total of 1511 patients treated between 01/10/2002 and 31/12/2014,129 patients treated with single agent anti- EGFR were identified, 75 had received prior bevacizumab. Demographics, performance status and tumour characteristics were similar between the 2 groups. 84% were confirmed KRAS exon 2 wild type. Prior treatment with bevacizumab did not impact DCR (35% vs 40%, p = 0.5065), median PFS (3.0 vs 3.0 months, p = 0.9460) or OS (8.6 vs 8.4 months, HR 0.95, p = 0.8073). Similarly, for bevacizumab treated patients, the time since last dose of bevacizumab to start of anti-EGFR ( &lt; 3 months (n = 26) vs 3-6 months (n = 17) vs &gt; 6 months (n = 32)) did not impact PFS (2.3 vs 3.6 vs 3 months) or OS (8.9 vs 10.1 vs 7.1 months, HR: 0.88, p = 0.82). Conclusions: There was no evident impact of previous bevacizumab treatment, or time from previous bevacizumab treatment, on the efficacy of single agent anti-EGFR therapy in a routine clinical practice cohort. Our data do not support the notion that prior bevacizumab renders tumors more or less sensitive to subsequent anti EGFR therapy.
Do locoregional recurrence and survival outcomes differ in women with node-negative, HER2-positive breast cancer treated with breast-conserving therapy versus mastectomy?
Authors: David John Peterson, Pauline Truong, Betro Sadek, Mina Shenouda, Alphonse Taghian, Cheryl Alexander
Journal: Journal of Clinical Oncology (2013)

69 Background: Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer subtype is an adverse prognostic factor, it is unclear whether there are differences in outcomes according to the type of locoregional treatment used in this population. This study compared locoregional recurrence and survival outcomes in women with node-negative, HER2-positive breast cancer treated with Breast Conserving Therapy (BCT) versus Modified Radical Mastectomy (MRM). Methods: Independent datasets from the BC Cancer Agency (BCCA) and the Massachusetts General Hospital (MGH) were pooled and analyzed. Study subjects included 748 patients between 2003-2009 with pT1-2, N0, M0 Her2+ breast cancer, treated with BCT or MRM. Standard clinico-pathologic factors were analyzed. Kaplan-Meier locoregional recurrence (LRR), breast cancer specific survival (BCSS) and overall survival (OS) were compared between cohorts treated with BCT vs. MRM. Multivariable analysis (MVA) with Cox regression modeling was performed to evaluate the prognostic significance of type of locoregional treatment on outcomes. Results: Median follow-up time was 4.2 years for BCCA and 6.0 years for MGH. Comparison of clinico-pathologic factors according to type of locoregional treatment found that patients treated with MRM had higher proportions of grade 3 histology (69% vs. 60%, p = 0.004) and PR-negative disease (56% vs. 44%, p = 0.008) and lower rates of endocrine therapy (51% vs. 64%, p &lt;0.001) and herceptin therapy (50% vs. 57%, p = 0.04). There were no significant differences between BCT and MRM groups in 5-year Kaplan-Meier LRR (2.0% vs. 1.7%, p=0.88), BCSS (97.2% vs. 96.1%, p=0.70), and OS (95.5% vs. 93.4%, p=0.19). On MVA, BCT and MRM were associated with similar LRR, BCSS, and OS. The only factor associated with reduced OS was T2 disease (HR 3.1, p=0.01). Conclusions: In this multi-institutional study, no significant outcome differences were found among women with T1-2 N0, HER2-positive breast cancer treated with BCT or MRM. Breast conserving therapy is safe in this population, providing high rates of locoregional control and survival equivalent to mastectomy.
Effects of gemcitabine and stereotactic body radiotherapy on quality of life in locally advanced pancreatic cancer.
Authors: Avani Satish Dholakia, Daniel Tandel Chang, Karyn A. Goodman, Elizabeth Sugar, Amy Hacker-Prietz, Laurie Ann Columbo, Mary E Griffith, Aaron Tyler Wild, Shalini Moningi, Timothy M. Pawlik, George A. Fisher, Susannah G. Ellsworth, Albert Koong, Joseph M. Herman
Journal: Journal of Clinical Oncology (2014)

278 Background: Existing literature on the impact of radiation therapy for locally advanced pancreatic cancer (LAPC) on quality of life (QoL) is limited and is specific to standard chemoradiation. We prospectively investigated patient-reported QoL after treatment with fractionated stereotactic body radiation therapy (SBRT). Methods: Forty-nine patients with LAPC treated were prospectively enrolled in a clinical trial at 3 institutions. Participants received a total of 33 Gy in 6.6 Gy daily fractions using SBRT either upfront (N=5) or after a single induction cycle of gemcitabine (N=44), followed by post-SBRT gemcitabine until evidence of disease progression. Two validated questionnaires, the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and pancreatic cancer-specific QLQ-PAN26, were administered to patients prior to SBRT and at 4-weeks and 3 to 4-months following SBRT. Results: QoL questionnaires were available for 43 patients (88%) in the clinical trial at enrollment, of which 38 (88%) and 22 (51%) also had data at 4-weeks and 3 to 4-months following SBRT, respectively. There was no significant change in global QoL scores from enrollment at 4-weeks (p=0.682) and 4-months (p&gt;0.999) following SBRT. Patients demonstrated a significant improvement in pancreatic pain (p=0.001), body image (p=0.007) and jaundice (p=0.001) scores from the pre-SBRT values at 4 weeks following SBRT. The initial 4-week results were similar when restricted to those patients with both 4-week and 4-month QoL data (p=0.020) and jaundice (p=0.004); however, these symptoms had returned to enrollment levels by the 4-month follow-up. An improvement in body image (p=0.016) and decline in role functioning (p=0.002) were observed in patients with 4-month follow-up QoL questionnaires. Conclusions: LAPC patients undergoing SBRT experience no impairment in global QoL and have short-term improvements in symptoms commonly bothersome to this population including pancreatic pain, body image, and jaundice. Patients also experience a delay in impaired role functioning several months after treatment. These results warrant further investigation of SBRT for LAPC. Clinical trial information: NCT01146054.
A new modified sunitinib schedule for metastatic renal cell cancer (mRCC): A pilot study.
Authors: Sebastiano Buti, Maddalena Donini, Silvia Lazzarelli, Matteo Brighenti, Rodolfo Passalacqua
Journal: Journal of Clinical Oncology (2012)

471 Background: Oral sunitinib administration at 50 mg daily given for 4 weeks followed by 2 weeks off treatment (4+2 schedule) is a standard first line for mRCC treatment. About 20% of patients had to discontinue treatment permanently and 50% of patients are forced to reduce the doses due to adverse events [Motzer RJ, J Clin Oncol. 2009]. A meta-analysis showed that increase exposure to sunitinib is associated with improved clinical outcome [Houk BE, Cancer Chemother Pharmacol. 2010]. Methods: This is a pilot study in which consecutive mRCC patients admitted to our hospital who had at least a grade 2 toxicity with sunitinib, were switched to a modified schedule maintaining the same dose-intensity of 4+2 schedule: starting on Monday, 1 tablet (50 mg) a day for 5 consecutive days a week for 5 weeks and 1 tablet per day on days 1, 3 and 5 in the sixth week (28 tablets in 6 weeks), until disease progression. Primary end points were toxicity changes assessment and schedule feasibility, secondary end point was overall progression free survival (PFS). Results: Eight nephrectomized patient were enrolled: 6 males; median age 61; 37% good, 50% intermediate and 13% poor MSKCC risk; 3 patient pretreated; 6 clear cell histologies, 1 papillary and 1 undifferentiated histotypes. Median time from start therapy to switch was 7.4 months (range 1.4-16.1). Treatment delays and dose reductions were reduced from 50% to 25% and from 37% to 12% of patients respectively. The table shows the toxicity changes: there were no new toxicities. PFS was 16.3 months (CI 95% 5.6-23.4). Conclusions: This new modified schedule requires and deserves further studies. [Table: see text]
Clinical trial and basic investigation: Angiotensin II receptor blocker decelerates PSA failure after radical retropubic prostatectomy
Authors: H. Uemura, K. Hoshino, Y. Miyoshi, Y. Kubota, K. Noguchi, S. Takahashi
Journal: Journal of Clinical Oncology (2008)

14676 Background: Angiotensin II receptor (AT1 receptor) blockers (ARBs) are a class of antihypertensive agent. Based on our previous study that demonstrated ARBs can suppress cell proliferation of prostate cancer cells by inhibiting signal transduction pathways through the AT1 receptor (Mol. Cancer Ther. 4:1699, 2005), a clinical trial of an ARB for PSA failure after retropubic radical prostatectomy (RRP) was undertaken. We also investigated whether ARBs can inhibit prostate cancer incidence in transgenic rats (Tag rats) that develop prostate cancer. Methods: Fourteen patients who had undergone RRP and had PSA failure were enrolled in this study. Patient characteristics were: median study nadir of PSA =0.076 ng/mL (range 0.003–0.165), median duration from RRP to nadir PSA =59.5 days (26–448), median duration from nadir PSA to >0.2 ng/mL =468.7 days (35–2905). They were all started on olmesartan (OLM), an ARB, at the point when PSA was more than 0.2 ng/mL. PSA doubling time (PSA-DT) was compared between before and after OLM administration. In an in vivo study, Tag rats were treated with an ARB for 12 weeks, and cancer incidence and apoptosis of prostate glands were investigated. Results: Of 14 patients, 12 showed deceleration of PSA-DT by OLM treatment. Mean PSA-DT after treatment with OLM was 3.6 times (1349 days) that before treatment (372.7 days). Also, PSA-DT of patients treated with OLM was significantly longer than that of the control group who received no treatment from nadir PSA to 1.0 ng/mL. There was no relationship between the response to OLM and the pathological grade. In Tag rats, the ARB significantly suppressed prostate cancer incidence compared to that in non-treated rats, in a dose-dependent manner. Western blot analysis showed that MAPK phosphorylation was inhibited in prostate glands treated with ARB. Conclusions: From the above data, we believe that ARBs have novel ability to decelerate PSA-DT, and this treatment should be first undertaken in patients with PSA failure after RRP. No significant financial relationships to disclose.