tbuckley/cabot-search huggingface dataset:
Association between delays in adjuvant chemotherapy for stage III colon cancer and increased mortality.
Authors: Alex Bernard Haynes, Yj Chiang, Barry W. Feig, Yan Xing, George J. Chang, Y. Nancy You, Janice N. Cormier
Journal: Journal of Clinical Oncology (2012)

541 Background: Administration of adjuvant chemotherapy is the standard of care for stage III adenocarcinoma of the colon. There are conflicting data regarding the optimum interval for the initiation of adjuvant therapy and whether this affects survival. Methods: Patients were identified from the National Cancer Database (1998-2002) who received adjuvant chemotherapy after resection of stage III colon cancer. Multivariate analyses were performed to examine the associations between time interval from surgery to chemotherapy initiation and overall and relative survival. Relative survival was used as a surrogate for disease-specific survival. Results: 32,327 stage III colon cancer patients who received chemotherapy after surgery were identified. The relationship between timing of adjuvant chemotherapy and survival is reported in Table 1. Delay of chemotherapy beyond 8 weeks postoperatively was associated with an increased likelihood of death in a relative survival model, with a hazard ratio for death of 1.19 (95% CI: 1.11, 1.28) in the 8 to 12 week interval. Longer delays were associated with worse outcomes, with a 7.6% absolute decrease in relative survival. Other independent factors associated with reduced survival included gender, race, type of insurance, margin status, and tumor grade. Conclusions: Delay in the initiation of adjuvant therapy beyond eight weeks is an independent predictor of increased mortality. While other factors contribute to the risk of death from disease, chemotherapy delays may be preventable. Policy interventions should be developed to encourage the administration of chemotherapy within eight weeks of resection when indicated. Further effort should be expended to understand the etiology of and mitigate these delays. [Table: see text]
Understanding the role of physician assistants in oncology
Authors: A. C. Ross, M. Polansky, P. A. Parker, J. L. Palmer
Journal: Journal of Clinical Oncology (2008)

17509 Background: Recent analysis of US oncology work force commissioned by ASCO predicts a significant shortage of providers by 2020. One proposed option to ease this burden is increased utilization of non-physician clinicians. In the practitioner survey, oncologists utilizing PAs/NPs reported improved efficiency and patient care, as well as professional satisfaction. This was particularly true when PAs/NPs were used for “advanced activities”. Of 75,000 US PAs, 2.4% practice in oncology, with little information reported about their roles. Methods: A descriptive study was conducted using a web based survey from 11/7 - 12/14/07. Invited participants included all PAs listed in the national PA database (855) listing practice in med onc, hem/onc, rad onc, surg onc, pedi onc or pedi hem/onc and all PAs at UT M.D. Anderson Cancer Center (159). Ten letters were undeliverable, resulting in a total of 1004 PAs contacted. Results: The study produced a 30% participation rate. Of 301 respondents, most were female (4:1); average age 39. Average length of time working as a PA was 10 years, with mean of 6 years in oncology. Only 8% of respondents reported completing a postgraduate training program, while 87% reported direct mentorship by their supervising physician “very important” in obtaining their knowledge of oncology. Approximately half of the respondents felt it took 1 to 2 years to be “fully competent” in their practice of oncology. Specific responsibilities of PAs varied greatly, primarily depending on their oncology discipline. 65% (196) work in a medical oncology discipline: med onc, hem/onc, and pedi onc. Of these PAs in medical oncology, >70% write chemotherapy orders, most requiring physician co-signature and 83% prescribe schedule III-V controlled substances. Most perform procedures: 56% bone marrow aspiration/biopsy and 35% intrathecal chemotherapy administration. Further data was gathered regarding clinical duties, research and teaching. Conclusion: PAs working in oncology are utilized in multiple medical arenas and many assume high level responsibilities. With better understanding of their current role and addressing factors that limit utilization, PAs may play a key role to ensure that quality medical care is available for cancer patients for future decades. No significant financial relationships to disclose.
Influence of physical activity on the development of arm lymphedema after breast cancer surgery. A prospective, randomized controlled trial with a 2-year follow-up
Authors: A. Sagen, R. Kåresen, M. Risberg
Journal: Journal of Clinical Oncology (2008)

9542 Background: Arm lymphedema (ALE) is a well known complication after axillary clearance in breast cancer surgery. Postoperative rehabilitation has included restricted physical activities with the affected limb, but the rational for such restrictions and evidence to support these clinical guidelines have been lacking. The purpose of this randomized clinical trial was to evaluate the influence of physical activity involving the affected limb on the development of ALE and to examine predictive factors for ALE after breast cancer surgery. Methods: Women (n=204) aged 32 to 75 years who had complete axillary node dissection were randomized into a high-level activity group (HL) (n=104) with no restrictions in physical activities involving the affected limb, and a low-level activity group (LL) (n=100) with restrictions in physical activities involving the affected limb. Baseline measurements and follow-up tests were performed at 3 and 6 months, and 2 years after surgery. Primary outcomes were arm volume (ml), volume differences between affected and control arm (voldiff), and ALE defined as 10% increase in affected arm volume compared to control arm volume. ANCOVA for repeated measures with covariate for baseline values was used to evaluate changes between groups. Results: No significant differences between the HL and LL groups were found for arm volum, voldiff or ALE. Significant predictive factors for ALE were BMI > 25, surgery on the dominant side, and volume differences between the affected and the control arm at baseline > 1 ml (P<. 02). Conclusions: High physical activity level with the affected limb following breast cancer surgery with axillary clearance did not seem to influence the development of ALE. Predictive factors for ALE were BMI > 25, surgery on the dominant side and volume differences between the affected and control arm at baseline > 1 ml. No significant financial relationships to disclose.
The importance of total dose intensity in the treatment of primary central nervous system lymphoma
Authors: D. F. Kraemer, L. Angelov, N. D. Doolittle, T. Siegal, D. M. Peereboom, K. Jahnke, S. Bell, G. Barnett, J. McGregor, E. A. Neuwelt
Journal: Journal of Clinical Oncology (2008)

13004 Background: Chemotherapy effectiveness in treating malignant brain tumors (e.g. primary central nervous system lymphoma or PCNSL) is thought to improve as total dose intensity delivered to the tumor increases. This report assesses the impact of total dose intensity in a large case series of newly-diagnosed PCNSL patients. Methods: A previously-reported series of 149 PCNSL patients treated at four centers (Angelov et al, JCO 25:18S, 2007, abstract 2014) treated with a methotrexate-based regimen in conjunction with blood- brain barrier disruption (BBBD), without up-front whole brain radiotherapy was analyzed. The degree of disruption was recorded for each BBBD procedure. ECOG performance status, number of disruptions, and a cumulative degree-of-disruption score were used as time-dependent covariates in proportional hazards regression models (adjusted for potential confounders) to predict survival. Results: Mean number of disruptions was 14.0 (SD 7.8) and mean cumulative degree of disruption score was 44.3 (SD 27.5). Number of disruptions (hazard ratio 0.911, 95% CI: 0.880, 0.944) and cumulative degree of disruption score (hazard ratio 0.974, 95% CI: 0.964, 0.983) were significant predictors of survival. Controlling for age and performance status (at baseline value and as a time-dependent covariate) did not substantially change the hazard estimate or its p-value. Conclusions: These results support a dose response relationship between dose intensity and survival, in patients with PCNSL. Use of these predictors as time-dependent covariates avoids a survival bias that could otherwise result. Conclusion: There is a statistically significant association between total dose intensity and survival in these patients supporting the efficacy and importance of blood-brain barrier disruption for treating PCNSL patients. No significant financial relationships to disclose.
“She would be flailing around distressed”: Addressing the hidden crisis in the home of patients being treated for cancer.
Authors: Brook Calton, Nancy Shepard, Redwing Keyssar, Nicole Thompson, Kanan Patel, Virginia Dzul-Church, Helen Kao, Christine Ritchie, Michael W. Rabow
Journal: Journal of Clinical Oncology (2015)

147 Background: Metastatic cancer patients who have progressed on multiple lines of chemotherapy and/or have poor functional status are at risk for significant symptoms, ineffective treatments, and hospice under-utilization. Appreciating the full extent these patients’ struggles is challenging during brief oncology clinic visits. We describe Community Bridges (CB), a home-based palliative care program. Methods: The CB pilot featured a 3-person home-based palliative care MD, NP, and RN team. Patients with metastatic cancer and complex care needs ( &gt; 3 chemotherapy lines, ECOG ≥ 3, history of missed PC clinic appointments, and/or clinical trial participation) were offered 2 months of serial home visits and phone support. Symptom severity, satisfaction, and caregiver burden were assessed. Results: 18 patients enrolled. Mean age was 66. At baseline, 79% of patients reported mild-moderate pain, 43% severe fatigue, 38% moderate-severe depression, and 65% poor-fair QOL. Half of patients died within the 2-month program or within 3 months later. 35% of patients enrolled in hospice while in CB, with a LOS of 10 days. Caregiver burden was high. 60% of patients (n = 6) and 100% of caregivers (n = 7) agreed CB provided services not otherwise available. All would recommend the program to others. Participants reported CB helped them navigate the medical system and reduce stress. Caregivers reported CB helped their loved ones regain control of care. The CB team noted key program strengths were accurately identifying the patients’ home needs, communicating findings to oncologists, and intervening quickly when patients were at the end of life and/or actively dying. Conclusions: CB met patients in their final stages, when they were experiencing heavy symptom burden, functional decline, patient/caregiver distress, and risk of death. The CB team was able to assess and respond to changing needs during key transitions points, and report the realities at home to help inform oncologists’ treatments. Although CB was not designed as a “crisis service,” it often served in that role. Home-based palliative care programs like CB may bridge the gap for patients desiring ongoing cancer treatment but in need end-of-life services.
Impact of BRCA mutation test results in members of hereditary breast ovarian cancer (HBOC) families
Authors: C. Snyder, J. A. Lynch, P. Karatoprakli, S. Coronel, A. Trowonou, K. Metcalfe, S. A. Narod, G. Gong, H. T. Lynch
Journal: Journal of Clinical Oncology (2005)

1014 Background: Disclosure of BRCA mutation results may cause distress and in turn affect patient’s behavior, work and decision on cancer screening and management. Methods: Members (n=898) from 84 HBOC families who received their result and genetic counseling provided responses to their BRCA mutation test result. Findings from 395 responders (78 with breast cancer and a BRCA mutation; 20 with cancer but without a mutation; 90 without cancer but with a BRCA mutation, and 207 without cancer and without a mutation) were analyzed by Kruskal-Wallis, Dunn and Fisher’s exact tests. Results: Mutation-carriers regardless of their cancer status gave statistically higher emotionally laden scores than comparable non-carriers without cancer. Following mutation disclosure, 23% (36/154) underwent prophylactic bilateral mastectomy as compared to 5.5% (36/660) before mutation test disclosure (p<0.001). After mutation disclosure 51.5% (88/171) underwent prophylactic bilateral oophorectomy as compared to 26% (171/660) before mutation disclosure (p<0.001). No non-mutation carriers (n=352) chose prophylactic surgery after result disclosure. Alteration in screening behavior based upon BRCA mutation results are depicted in the table. A significant higher percentage of BRCA positive individuals who did not have annual ovarian ultrasounds before their result disclosure chose to do so after result disclosure as compared to their BRCA negative counterparts (p< 0.005). Similar findings were seen for annual CA-125 blood tests (p<0.001). Conclusion: These data harbor an important clinical translation as reflected by alterations in screening behavior and surgical prophylaxis in response to genetic counseling and BRCA mutation findings. No significant financial relationships to disclose.
Predictive factors of resistance to trastuzumab as neoadjuvant therapy in women with HER2-positive breast cancer.
Authors: Hiromitsu Jinno, Tomomi Sato, Maiko Takahashi, Tetsu Hayashida, Shigemichi Hirose, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2013)

168 Background: Despite clinical usefulness of trastuzumab, intrinsic or acquired resistance to trastuzumab is a common clinical phenomenon. However, the mechanisms of resistance to trastuzumab have not been fully elucidated. The objective of this study was to determine the possible mechanisms of resistance to trastuzumab as neoadjuvant therapy in women with HER2-overexpressing operable breast cancer. Methods: Patients with operable breast cancer received 12 cycles of weekly paclitaxel plus weekly trastuzumab before surgery. All tumors were HER2-positive by immunohistochemistry (IHC) or fluorescence in situ hybridization. Expressions of ER, PgR, Ki67, PTEN, phosphorylated IGF-1R (pIGF-1R) and MUC4 were performed by IHC in core needle biopsy samples at baseline. PIK3CA mutation status was evaluated by sequencing of PIK3CA exons 9 and 20 using PCR amplification and direct sequencing. Results: Thirty-seven patients were enrolled and assessable for clinical and pathologic responses. The pCR rate was 48.6% (18/37). Negative, moderate and strong membranous expression of MUC4 was observed in 3 (8.1%), 18 (48.6%) and 12 (32.4%) patients, respectively. Membranous staining for pIGF1-R was negative in 24 (64.9%) patients. PTEN loss was observed in 33.3% (8/24) of the tumor examined. PIK3CA sequence analysis of the 13 tumors identified 2 mutations in exon 20 and 2 mutations in exon 9, corresponding to a PIK3CA mutation frequency of 30.8%. MUC4 status did not affect the pCR rate. Although membranous pIGF1-R expression did not affect pCR rate in hormone receptor-positive patients (66.7% vs. 50.0%), hormone receptor-positive patients with positive membranous pIGF1-R tended to show higher pCR rate compared with negative pIGF1-R (41.2% vs. 0%). PTEN loss and/or PIK3CA mutation were not significantly associated with pCR rate. Conclusions: These data indicate that aberrant downstream signaling caused by loss of PTEN and/or PIK3CA mutation, alternative signaling from IGF-1R and masking with MUC4 were not important mechanisms of resistance to trastuzumab.
Association of morphologic response with progression free survival in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy: HGCSG0802.
Authors: Satoshi Yuki, Hiroshi Nakatsumi, Hideyuki Hayashi, Hiraku Fukushima, Takashi Kato, Takashi Meguro, Michio Nakamura, Ichiro Iwanaga, Kazunori Eto, Atsushi Sato, Hiroyuki Okuda, Ayane Oba, Takuto Miyagishima, Osamu Muto, Satoshi Yabusaki, Noriyuki Miyamoto, Kohsuke Kudo, Naoya Sakamoto, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2015)

743 Background: It was reported that an optimal morphologic response to preoperative chemotherapy was associated with better overall survival (OS) in patients (pts) with colorectal liver metastases (CLM). We investigated association of morphologic response with progression free survival (PFS) in pts with unresectable CLM from HGCSG0802 observational cohort study in pts with mCRC treated with first-line bevacizumab (BV)-based chemotherapy. Methods: The objective of HGCSG0802 was to evaluate PFS, OS, time to treatment failure (TTF), response rate (RR), safety, etc. The key eligibility criteria were evaluable lesions, older than 20 years old, ECOG PS 0-2. Pts with CLM underwent contrast-enhanced CT at the start and every 8-weeks of BV-based chemotherapy. In this analysis, three blinded, independent radiologists evaluated images for morphologic response, based on metastases changing from heterogeneous masses with ill-defined margins into homogeneous hypoattenuating lesions with sharp borders. Association of morphologic response and pts characteristics, RR, and PFS were evaluated. PFS was analyzed with Kaplan-Meier method, log-rank test, and Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 73 pts with CLM were evaluable for morphologic criteria. Eighteen pts (24.7%) had optimal morphologic response (OR), 31 (42.5%) had incomplete (IR), and 24 (32.9%) had no response (NR). The pts characteristics between those with OR, IR and NR were generally balanced. The median TTF was 7.2 months in NR versus 7.2 months in IR versus 6.8 months in OR (HR (OR/NR) = 0.91, HR (OR/IR) = 0.90; p = 0.93). RR was 77.8% in OR versus 64.5% in IR and 58.3% in NR (p = 0.528). The median PFS was 8.3 months in NR versus 8.5 months in IR versus 9.1 months in OR (HR (OR/NR) = 0.72, HR (OR/IR) = 1.04; p = 0.420). Conclusions: In this analysis, morphologic response might not be a prognostic marker in first-line BV-based chemotherapy in pts with CLM.
Surrogate endpoint for prostate cancer-specific survival: Validation from an analysis of Radiation Therapy Oncology Group Protocol 92–02
Authors: R. Valicenti, M. Desilvio, G. Hanks, A. Porter, H. Brereton, W. Shipley, H. Sandler
Journal: Journal of Clinical Oncology (2005)

4549 Background: A requirement of a surrogate endpoint for prostate cancer-specific survival (PCSS) is its validation for a cohort of prospectively treated patients. We applied Prentice’s criteria to determine if prostate-specific antigen doubling time (PSA-DT) fulfilled this requirement for the prostate cancer (T2C-T4 and PSA level < 150 ng/ml) patients treated on Radiation Therapy Oncology Group (RTOG) Protocol 92–02. Methods: We calculated PSA-DT assuming first-order kinetics for a minimum of three rising PSA measurements after time of randomized treatment (hormonal cytoreduction and radiation therapy without or with adjuvant androgen deprivation (arm 1 vs. arm 2)). We defined incidence of PSA-DT <3, <6, <9, and < 12 months as time-to-event endpoints. Using Kaplan-Meier methods and Cox proportional hazards model, we tested this definition of a surrogate for PCSS by Prentice’s criteria (table). We evaluated: if randomized treatment predicted PCSS (1) and PSA-DT (2) and; if PSA-DT predicted PCSS (3) and was independent of randomized treatment (4a, b). Results: We analyzed all 1514 eligible patients. Median follow-up time was 71 months (142 prostate cancer deaths). Randomized treatment predicted PCSS (1) and PSA-DT <6, <9, or <12 (2). These three PSA-DT cutoffs also predicted PCSS (3). However, only for PSA-DT <12, did randomized treatment have no significant effect on PCSS (4a, b). Conclusions: Post-treatment PSA-DT <12 months met all of Prentice’s criteria for surrogacy. For the first time, this was accomplished for a prospectively studied patient population, and justifies strong consideration for PSA-DT< 12 months as a surrogate endpoint for prostate cancer mortality. Supported by NCI grants: RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115 No significant financial relationships to disclose.
Association between serum adiponectin and prostate cancer risk
Authors: S. Jacobus, D. J. Sher, M. M. Regan, J. Chamberland, W. K. Oh, C. Mantzoros
Journal: Journal of Clinical Oncology (2008)

5147 Background: Adiponectin is a fat adipokine that has been linked with several hormonally-active adenocarcinomas. Recent studies have suggested a relationship between serum adiponectin and hormone-dependent prostate cancer (PCA), supported in part by an association between BMI and prostate cancer grade. We evaluated this potential relationship. Methods: PCA patients evaluated at Dana-Farber Cancer Institute (DFCI) between 2001 and 2006 who enrolled in a prospective serum banking protocol and were without prior hormonal therapy and/or metastatic disease were eligible. Serum adiponectin levels were ascertained and clinical data were contributed by the DFCI prostate cancer Clinical Research Information System (CRIS) database. Associations between adiponectin quartiles and categorical patient characteristics were assessed using the chi-square test (χ2). Spearman correlation coefficients were used to quantify associations between continuous variables. High-grade disease was defined as biopsy or radical prostatectomy (RP) Gleason score (GS) of ≥ 7. Logistic regression models were used to assess the relationship between high-grade disease and adiponectin levels while adjusting for other potential prognostic variables. Results: There were 539 pts included in this study, 199 of whom underwent RP. Median age was 60 yrs with 94% of pts white. Median PSA was 5.1 ng/dL (IQR 4.2–7.3). 21% of cancers were clinical T2 or higher. GS ≥7 was seen in 47% of pts at diagnosis and 51% of RP pts. Spearman correlation coefficients showed weak associations of adiponectin with PSA and age, but a stronger and significant inverse association between BMI and adiponectin was observed. Higher PSA, higher age, and higher BMI were significantly associated with increased odds of biopsy GS at diagnosis ≥7, but adiponectin was not. There was a significant inverse relationship (p=0.014) between RP GS and adiponectin dichotomized at the median. Although, adiponectin analyzed in quartiles showed a non-monotonic pattern. Dichotomized adiponectin remained significant after adjusting for BMI, PSA and age. No significant interaction between BMI and adiponectin was observed. Conclusions: In a subset of RP patients, lower adiponectin was inversely associated with prostate cancer grade, independent of BMI, age and PSA. No significant financial relationships to disclose.