tbuckley/cabot-search huggingface dataset:
The availability/accessibility gap of palliative care and supportive care services at 40 National Cancer Institute-designated cancer centers.
Authors: Kathryn Hutchins, Geoffrey Hamlyn, Abby Johnston, Rishonda Thomas, James Tian, Arif Kamal
Journal: Journal of Clinical Oncology (2016)

122 Background: All NCI-designated, comprehensive cancer centers report having consultative palliative care services alongside six other supportive care services. Inaccuracies in the understanding of these services among frontline office staff may undermine their accessibility to patients. We investigated how easily new patients could access these services when first contacting a major cancer center. Methods: We used a ‘mystery shopper’ format to simulate calls made by a family member of a recently diagnosed patient. We used a standardized call script, describing a female patient, age 58, recently diagnosed with inoperable liver cancer. We called each center four times on different days and evaluated quantitative and qualitative components. Descriptive statistics were calculated for each quantitative measure. Results: We placed 160 calls to 40 NCI-designated cancer centers. 38.2% of callers were unable to receive complete information about supportive care services. Overall, only 37.6% of callers (60.8% of those reaching someone who could answer questions) were told all 7 supportive care services were offered. In 9.5% of calls, call recipients gave an answer other than “yes” to whether the cancer center offered palliative care. Callers were told regarding palliative care: that it was for end of life patients only (2 calls), that there weren’t doctors who focused on symptom management (3), its availability depends on review of medical records (2), or that the call recipient was unsure either of the availability of palliative care (10), or did not know what the term meant (2). Availability responses other than “yes” were obtained in the following frequencies: multidisciplinary approach (14.6%), patient navigation (12.1%), genetic assessment (9.5%), psychological services (7.6%), and cancer education services (6.4%). Conclusions: Despite the stated availability of seven key supportive care services, accessibility was limited in one-third of calls. In about 10% of cases where a person was reached, the call recipient was unable to confirm that palliative care was offered. Further research is needed to close the availability vs. accessibility gap in oncology palliative and supportive care.
The presence of bone (BM) and concomitant non-bone metastases (cNBM) significantly worsens the 2-year overall survival (OS) in breast cancer (BC) patients (PTS): Update of results in the moon study
Authors: M. E. Cazzaniga, L. Dogliotti, V. Torri, R. Labianca, S. Barni, S. Cascinu, L. M. Pasetto, R. Rosso, G. Gasparini, P. Conte
Journal: Journal of Clinical Oncology (2005)

774 MOON study aimed at investigating presentation, treatment and evolution of BM in BC pts and comparing them to metastases (MTS) at different sites. Four-hundred and fifty-nine BC pts have been enrolled: median age was 60.2 years (28–94), 54.4% had only BM, while 18.8% and 26.9% presented previous (pNBM) or concomitant non bone metastases (cNBM) at baseline. OS, time to new skeletal events and time to new BM and NBM have been estimated after a median follow up of 28 months. The proportion of surviving pts with cNBM at 1-year was very close to that of BM ones (0.80 vs 0.87); on the contrary, the 2-year estimated survival distribution was significantly worse for the cNBM group in comparison to that of BM pts: 0.56 (0.46–0.67) vs 0.74 (0.67–0.80), respectively. In addition, many more pts in the BM group had the probability to be free of new metastases at sites different from bone in comparison to cNBM pts, both at 1 and 2 years: 0.75 (0.69–0.81) vs 0.59 (0.49–0.69) and 0.54 (0.46–0.61) vs 0.28 (0.19–0.38), respectively. No difference was observed between the two groups in terms of time to new skeletal events (0.68 vs 0.67) and time free from new BM (0.52 vs 0.47). In conclusion, the presence of cNBM significantly worsened the 2-year estimated OS and the time free of new non bone metastases in BC pts. No significant financial relationships to disclose.
Fludarabine and cyclophosphamide combination in the treatment of patients with indolent non-follicular B-cell non-Hodgkin’s lymphomas. Results of a phase II trial of the Gruppo Italiano per lo Studio dei Linfomi (GISL).&gt;
Authors: M. Federico, S. Luminari, M. Brugiatelli, M. Goldaniga, S. Sacchi, F. Merli, C. Stelitano, A. Bagnulo, M. Rizzo, L. Baldini
Journal: Journal of Clinical Oncology (2005)

6615 Background: Indolent non follicular lymphomas (INFL), comprise a rather heterogeneous subgroup of lymphomas, including small lymphocytic lymphoma (SLL), Immunocytoma (IC) and marginal zone lymphomas (MZL). In April 2002 we started a phase II trial aimed to verify the efficacy of Fludarabine and Cyclophosphamide (Flu-Cy) combination in this subset of NHL, in terms of response, survival and safety. Methods: Patients were enrolled according to the following inclusion criteria: diagnosis of SLL, IC, MZL, supported by morphologic, phenotypic and molecular data; non previous treatment; have active disease defined by the presence of anemia (Hb < 11 g/dL) or thrombocytopenia (Plt <100 x 109/l) or bulky disease or rapidly increasing lymphocytosis or enlarging masses. Treatment consisted of Fludarabine 25mg/sqm iv days 1–3 and cyclophosphamide 250mg/sqm IV days 1–3, to be repeated every 28days for 6 cycles; an intermediate evaluation of response after 3 cycles was planned and an adequate anti-infective prophyilaxis was mandatory: the use of G-CSF was not mandatory. Results: As of December 2004, 49 patients were registered into the trial; two patients were excluded from the study due to incorrect histology. Median age of the remaining 47 patients was 63 years (Range 39–74), M/F ratio was 1.7. All patients had stage IV disease; 9 patients (19%)presented with B symptoms. Anemia (Hb <11 g/dl) was present in 29%, elevated LDH in 32% elevated β2microglobulin in 63%. At the time of the present analysis 35 patients completed the treatment program achieving 50% CRs and 47% PRs. Three patients died during treatment, one after the 2nd cycle due to erosive pulmonary aspergillosis, two due to bone marrow aplasia occurred after the 4th cycle. Overall, grade III or IV neutropenia was observed in 38% of the patients and infections in 4 (12%). After a median follow up of 14 months 2years PFS was 80% while EFS was 56%. Conclusions: Flu-Cy combination is an effective treatment for patient with INFL but is also associated with a relevant toxicity profile. No significant financial relationships to disclose.
Use of pegilated liposomal anthracycline (PLD) in clinical practice: Results and toxicity
Authors: V. Lorusso, G. Console, P. Nardulli, C. Calabrò
Journal: Journal of Clinical Oncology (2005)

5180 Background: Pegilated liposomal doxorubicin (PLD) is considered a less toxic drugs as compared to conventional doxorubicin. The drug has the following indications: AIDS related Kaposi sarcoma, pretreated ovarian carcinoma and breast cancer patients (pts) at risk of cardiotoxicity. Methods: We have reviewed all the cases treated with PLD in our Institute in the last 3 years, out of clinical studies, in order to define the results and toxicity of these very expensive drug in daily clinical practice. Results: From Jan 2001 to Dec 2003 we have treated 108 pts with the following characteristics: 103 women and 5 men, median age 63 yr (range 38–82), 51 ovarian, 37 breast, 5 sarcoma, 4 endometrial, 4 NHL, 3 Kaposi, 2 biliary tract, 1 thyroid and 1 mesothelioma. With regard to ovarian cancer series, 36 pts have been treated with PLD as single agent, 11 in combination with oxaliplatin, 3 with paraplatin and 1 with gemcitabine, respectively. Responses were observed in 7 pts (3 CR + 4 PR) out of 51 pts (14%) and SD was observed in 12 (23%) of pts. With regard to breast cancer pts, 6/37 (16%) PR and 11/37 (29%) SD were observed in this series of heavily pretreated patients. In fact, all breast cancer pts had previously received anthracyclines and most of them also taxanes. Of the 4 NHL patients, 3 responded, whereas no one of the other tumor types responded. With regard to the toxicity, 28 out of 108 (26%) pts showed either palmo-plantar erytrodisestesia (PPD) at various degree or any form of cutaneous toxicity or first dose reaction which prevented drug continuation in 11 (10%) pts. Moreover, mucositis was observed in 24% of pts treated with doses over 40 mg/mq every 3 weeks, whereas neutropenia and alopecia were rarely complained. Cardiac toxicity was observed in 3/108 (3%) pts who were heavily pretreated with conventional anthracyclines at dosage of 755, 875 and 1234 mg/mq PLD respectively. Conclusions: From our retrospective study we learnt that the cost-effectiveness of PLD is high, and that toxicity, other than cardiac hematologic and alopecia, is also severe in heavily pretreated pts. On the other hand, the low incidence of cardiovascular events should advice to a better selection of pts to submit to PLD and to an earlier use in the course of the neoplastic disease. No significant financial relationships to disclose.
Phase I Study of On 01910.Na (rigosertib), a Multikinase PI3K Inhibitor in Relapsed/Refractory B-Cell Malignancies
Authors: Mark Roschewski, Mohammed Farooqui, Georg Aue, Clifton C. Mo, Janet Valdez, Susan Soto, Patricia Perez-Galan, Francois Wilhelm, Adrian Wiestner
Journal: Blood (2012)
Molecular dissection of effector mechanisms of <i>RAS</i>-induced resistance to monoclonal anti-EGFR antibodies.
Authors: Stefan Kasper, Frank Breitenbuecher, Jeannette Markowetz, Henning Reis, Johannes Meiler, Kurt W Schmid, Tanja Trarbach, Martin H. Schuler
Journal: Journal of Clinical Oncology (2012)

501 Background: RAS mutations are negative predictors of efficacy of anti-EGFR antibodies in patients with colorectal cancer (CRC). Oncogenic RAS activates the MAPK- and PI3K/AKT pathways, which are considered the main effectors of resistance. However, the relative impact of these pathways and their downstream effectors in RAS-mutant CRC is less defined. To this end we conducted functional studies using transgenic cancer models in vitro and in vivo. In addition, we analyzed pathway activation in primary tumor samples from metastatic CRC patients. Methods: Anti-EGFR-antibody sensitive cancer cell lines were retrovirally transduced to stably express (i) oncogenic RAS, (ii) conditionally active mutant RAF-1 or (iii) AKT. The impact of oncogene expression on cell proliferation, induction of apoptosis, clonal survival and tumor growth in NOD/SCID mice was analyzed in relation to treatment with cetuximab or panitumumab. Cell lines with endogenous KRAS or PI3KCA mutations were used as additional controls. Primary tumor samples from 47 patients with metastatic CRC were immunohistochemically analyzed for activation of the MAPK and PI3K/AKT pathways in relation to KRAS status. Results: Transgenic RAS, RAF-1 and AKT protected anti-EGFR-sensitive CRC cells against anti-proliferative and pro-apoptotic effects of the antibodies in vitro and in vivo. This was in line with immunohistochemical analyses of primary tumour samples, which revealed a strong correlation of MAPK and PI3K/AKT pathway activation and mutant KRAS (regression 0.921, p&lt;0.0001). Sustained activation of both pathways caused upregulation of anti-apoptotic BCL-2 proteins. Transgenic expression of these BCL-2 proteins could substitute oncogenic RAS in mediating antibody resistance. Cotreatment with BH3 mimetics neutralizing anti-apoptotic BCL-XL and BCL-2 sensitized RAS-mutant cancer cells to anti-EGFR therapy. Conclusions: Activation of the MAPK and PI3K/AKT pathways mediates resistance to anti-EGFR therapies in cancer models in vitro and in vivo. Simultaneous or cross activation of both pathways is observed in KRAS mutant primary CRC. These results may guide clinical strategies to overcome RAS-mediated antibody resistance.
Effect of body mass index (BMI) and body surface area (BSA) on outcomes in early-stage colon cancer (CC).
Authors: S. Alipour, R. Woods, H. J. Lim, S. Gill, H. F. Kennecke, C. Speers, C. J. Brown, W. Y. Cheung
Journal: Journal of Clinical Oncology (2011)

3615 Background: Research suggests that diet and physical activity may influence the risk of recurrence and survival in patients (pts) diagnosed with early stage CC. Whether this association is mediated through an effect on weight is as yet unclear. Our aims were to 1) assess the impact of BMI and BSA on outcomes in CC, 2) evaluate if the effect of obesity is modified by stage and adjuvant treatment, and 3) compare the utility of BMI vs BSA in predicting outcomes. Methods: Using a population-based cohort from 2001 to 2005, we compared 3-year disease-specific survival (3yr DSS) and 5-year overall survival (5yr OS) rates among early stage CC pts with different BMI and BSA. Cox proportional hazard models were constructed to explore the relationships between different body compositions and outcomes, while controlling for confounders. Results: We included 1,009 pts. At baseline, 463 pts were considered normal weight (BMI <25 kg/m2), 356 overweight (BMI 25-30 kg/m2) and 190 obese (BMI >30 kg/m2). Using Mosteller formula, 752 pts had normal BSA (<2 m2) and 257 had high BSA (≥2 m2). Obese pts experienced similar 3yr DSS (85.6 vs 82.9%, p=0.39) and 5yr OS (63.2 vs 64.5%, p=0.85) when compared to non-obese pts. Likewise, individuals with high BSA had similar outcomes as those with normal BSA (86.7 vs 82.3%, p=0.63 for 3yr DSS and 66.7 vs 63.4%, p=0.45 for 5yr OS). Cancer stage and receipt of adjuvant treatment did not modify the effect of BMI or BSA (Table). In Cox models, advanced age, male gender, stage III disease and poor performance status correlated with worse DSS and OS outcomes, but BMI and BSA did not. Conclusions: Obesity as measured by either BMI or BSA does not appear to influence DSS and OS in early stage CC. Diet and exercise exert their effects on CC outcomes likely through mechanisms other than weight reduction. Survival rates based on BMI and BSA. Outcome Subgroup BMI BSA Nonobese Obese P value BSA < 2.0 BSA ≥ 2.0 P value 3-year DSS rate Stage II 88.8 88.6 0.09 87.3 94.3 0.37 Stage III 77.1 82.4 0.70 76.8 82.3 0.68 No AT 84.3 86.6 0.26 83.0 90.1 0.16 AT 81.7 85.1 0.90 81.6 84.6 0.67 5-year OS rate Stage II 69.6 64.9 0.21 68.4 70.7 0.74 Stage III 58.2 59.2 0.38 57.3 61.5 0.38 No AT 65.3 59.6 0.39 62.9 70.2 0.21 AT 63.7 65.1 0.77 63.8 64.5 0.87 Abbreviation: AT, adjuvant therapy.
Management of breast cancer after childhood cancer and Hodgkin’s lymphoma.
Authors: M. Terenziani, S. Viviani, M. Massimino, A. Moliterni, M. Gennaro, L. Gandola, L. Boschetti, S. Catania, G. Cefalo, A. Di Russo, G. Goisis, G. Mariani, F. Spreafico, M. Zambetti, P. Valagussa, G. Bonadonna
Journal: Journal of Clinical Oncology (2011)

1566 Background: The risk of developing a secondary breast cancer (SBC) among women receiving chest radiotherapy (RT) for pediatric cancer and Hodgkin lymphomas (HL) is well established. The present study analyzes the clinical characteristics, pathology, management and prognosis of BC occurring after RT. Methods: From 1980 to 2010, 80 cases of SBC in a series of 76 survivors were diagnosed. These patients were treated from 1965 to 1992 with RT +/- chemotherapy for pediatric cancer or HL at Milan Cancer Institute. The histology, grading, nodal status, hormone receptor status, stage of the SBC, type of chemotherapy and surgery, disease free and overall survival were analyzed. Results: The median age at diagnosis of first neoplasms and of SBC was 18 and 38 years, respectively. The main histological features and the hormone receptor status paralleled the frequency observed in the case series of primary BC treated in the same Institution in the similar period of time. 67% of the tumors had ductal histology, 62% had positive estrogen receptor, 50% presented with pN0 and 68% with pT1 tumors. The incidence of bilateral synchronous SBC was 5%. In 59% of patients (41) adjuvant chemotherapy was administered, including antracyclines in 43% of this subgroup, followed by endocrine therapy in hormone positive receptor tumors only. Conservative surgery was feasible in 43 women (56%) and despite prior chest irradiation, subsequent breast RT was delivered in 33 of them. The five year disease free survival, overall and specific BC survival were 47%, 78% and 79%, respectively. Conclusions: Clinical characteristics, pathology and outcomes of SBC among this series of young women are similar to those observed in primary BC. Conservative surgery and repeat irradiation is also possible, without tissue necrosis. Despite previous therapies for their first malignancy, in a specialized institution patients with SBC can be managed in the same way as primary BC and carries similar chances of cure.
Final results of a phase I trial of PR104, a pre-prodrug of the bioreductive prodrug PR104A, given weekly to solid tumor patients.
Authors: M. J. McKeage, Y. Gu, W. R. Wilson, A. Hill, K. Amies, T. J. Melink, M. B. Jameson
Journal: Journal of Clinical Oncology (2010)

e13057 Background: The phosphate ester PR104 is rapidly converted in vivo to the alcohol PR-104A, a nitrogen mustard prodrug that is metabolized to hydroxylamine (PR104H) and amine (PR-104M) DNA crosslinking agents by one-electron reductases in hypoxic cells and by aldo-keto reductase 1C3 independently of oxygen. In a previous phase I study using a q 3 week schedule the maximum tolerated dose was 1,100 mg/m2 and neutropenia was dose-limiting. Methods: Patients (pts) with advanced solid tumors received PR104 as a 1-hour intravenous infusion on days 1, 8, and 15 every 28 days with assessment of pharmacokinetics on cycle 1 day 1. Results: A total of 26 pts were enrolled (16 male/10 female; median age 58 yrs [range 30 to 70 yrs]) who had received a median of 2 prior chemotherapy regimens (range, 0 to 3) for melanoma (6 pts), NSCLC (3 pts), sarcoma (2 pts), glioblastoma (2 pts), or other solid tumors. PR104 was administered at 135 mg/m2 (3 pts), 270 mg/m2 (6 pts), 540 mg/m2 (6 pts), 675 mg/m2 (7 pts), and 900 mg/m2(4 pts) for a median of 2 treatment cycles (range, 1 to 7 cycles). Dose-limiting toxicities (DLTs) during cycle 1 included grade 4 thrombocytopenia at 540 mg/m2 (1 of 6 pts) and grade 4 thrombocytopenia and neutropenia at 900 mg/m2 (2 of 4 pts). At an intermediate dose of 675 mg/m2, there were no DLTs in a total of 7 pts given 12 treatment cycles. Other toxicities included anaemia, fatigue, and nausea. At 675 mg/m2, the PR104A plasma concentration (Cmax) and exposure (AUC0-inf) were 9.91±2.61 μg/mL and 11.09±3.05 μg.h/mL, respectively (mean± SD; n=5). The major PR104A metabolite was the O-glucuronide PR104G (Cmax 6.58±3.70 μg/mL, AUC0-inf 8.16±5.35 μg.h/mL), with lower levels of PR104H (Cmax 0.32±0.13 μg/mL, AUC0-inf 0.45±0.11 μg.h/mL) and PR104M (Cmax 0.050±0.027 μg/mL, AUC0- inf 0.074±0.031 μg.h/mL). Conclusions: The MTD and recommended phase II dose for single agent PR104 weekly administration is 675 mg/m2/week for 3 weeks on a 28 day cycle. Higher dose intensity (1.4-fold) was achieved with weekly than with q 3 week dosing. Weekly PR104 administration may be suitable for clinical evaluation of its single-agent activity or combination with radiotherapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Proacta Proacta Proacta Proacta
Effect of continuous adjuvant chemotherapy and protracted treatment on recurrence and survival in resected pancreatic adenocarcinoma.
Authors: S. Hashimoto, T. Oda, K. Yamada, Y. Ohara, A. Kobayashi, K. Fukunaga, S. Murata, R. Sasaki, N. Ohkohchi
Journal: Journal of Clinical Oncology (2010)

e14676 Background: Adjuvant chemotherapy with gemcitabine (GEM) may be a standard theraputic strategy for surgically resected patients with pancreatic adenocarcinoma (PAC), as demonstrated by ESPAC-1 and CONKO-001 studies. Our institute had also introduced it since 2002. We noticed two distinct survival subgroups ie. A short-term survival case group (SG) and a long-term survival case group (LG) existed among our series. The purpose of present study was to reveal the clinicopathologic characters of SG and LG, and pursue the therapy strategy for the increase in a long-term survival case. Methods: We designed single institutional one-arm prospective adjuvant therapeutic strategy at 2002 to surgically resected PAC patients. Patients were expected to receive 3 out of every 4 week of once a week 1,000 mg/m2 GEM for at least 6 month after the surgery, and it should continued as much as possible. As for surgical procedure, extended lymphadenectomy and nerve plexus dissection were refrained and standard D2 dissection was performed. When local recurrence or metastatic diseases were evident, second line chemotherapy with oral S-1 was admitted. A total of 52 patients (male: 26, female: 26) were subjected to this protocol between 2002 and 2008. Eight cases (male: 4, female: 4) were picked up as SG (fated less than one-year) and 9 cases (male: 4, female: 5) were categorized as LG (three-year or more survival case). The clinicopathologic characters of two groups were compared. Results: Median survival time (MST) of our 52 cases was 23.4 months. The median of disease-free survival was 4.6 months for SG and 33.8 months for LG, respectively. The factors revealed to be different among two groups were pathological carcinoma retention, postoperative complication, compliance of 6 course of GEM and recurrence pattern. It should be noted that additional local therapies, including 2 cases of lung metastasis resection and 2 cases of local radiation, were applied in LG. Conclusions: Continuous adjuvant chemotherapy with GEM to PAC may confer a prognosis equivalent too or better to 6 months limit protocols. Attractive treatment to limited local or metastatic recurrence may provide survival benefit. No significant financial relationships to disclose.