tbuckley/cabot-search huggingface dataset:
Intensity-modulated radiotherapy for esophageal cancer: Analysis of toxicity and outcomes.
Authors: N. Kurshan, D. Ilson, M. A. Shah, D. P. Kelsen, A. Y. Ho, Z. Zhang, Q. Mo, K. A. Goodman
Journal: Journal of Clinical Oncology (2010)

4112 Background: Esophageal irradiation is limited by the radiosensitivity of surrounding tissues. Intensity-modulated radiation therapy (IMRT) allows for more conformal dose distributions; however, lower doses may be distributed to larger volumes of lung parenchyma, leading to elevated risks of pulmonary toxicity. We assess the acute and late toxicities and clinical outcomes of patients with esophageal cancer receiving pre-operative or definitive chemoradiotherapy (CRT) using IMRT. Methods: 65 esophageal cancer patients treated with CRT using IMRT from 3/07 to 5/09 at MSKCC were analyzed. 36 (55%) patients had adenocarcinoma and 29 (45%) squamous cell carcinoma. Two-thirds (65%) were located in the distal esophagus or GE junction, 20% were mid-thoracic and 15% upper thoracic or cervical. Patients were predominantly male (74%) with a median age of 68 years (range, 36-95 years). All patients received concurrent CRT, with the majority of patients (86%) receiving induction chemotherapy prior to CRT; median radiation dose was 5,040 cGy. 40% (n = 26) of patients underwent surgical resection. A Cox proportional hazards model was used for the analysis of overall survival (OS), and competing risks analysis was used for the analysis of local failure (LF) and distant metastasis (DM) outcomes. Results: All but one patient completed the prescribed course of radiotherapy; 21 patients (32.3%) required a treatment break. 24 patients (37%) had grade 3+ acute toxicity: hematologic (n = 12), GI (n = 10), skin (n = 1), pulmonary (n=1). There have been no grade 3+ late toxicities. With a median follow-up of 13.3 months for surviving patients, 1-year OS was 83.3% and the cumulative incidences of LF and DM were 43% and 28%, respectively. Nodal status and surgical resection were predictors of DM (p = 0.01) and LF (p=.05), respectively. Conclusions: CRT is well tolerated using IMRT, with 98% of patients completing the full course of radiotherapy and 50% of acute grade 3+ complications related to hematologic toxicity. Thus far, there have been no late grade 3+ pulmonary toxicities. IMRT may facilitate dose escalation for esophageal cancer without increasing normal tissue damage, ultimately improving outcomes for patients receiving CRT for this disease. No significant financial relationships to disclose.
“Debulk or not debulk?” An answer to an hamletic dilemma using a multi-institutional risk-adjusted model for evaluation of outcomes
Authors: G. D. Aletti, E. L. Eisenhauer, A. Santillan, A. Axtell, G. Aletti, C. Holschneider, D. S. Chi, R. E. Bristow, K. C. Podratz, W. A. Cliby
Journal: Journal of Clinical Oncology (2008)

5541 Background: Surgical outcomes for advanced ovarian cancer (AOC) cannot be meaningfully assessed without adjusting for extent of disease, endogenous patient factors and processes of care. We aimed to define the factors important in determining residual disease (RD) and overall survival (OS) in AOC Methods: Patient status, intra-operative findings and outcomes were assessed in 576 consecutive patients with AOC from 4 different tertiary centers. Tumor extent (TE) was stratified into 3 groups. Extent of surgery was categorized using a surgical complexity score (SCS). Primary outcomes were RD and OS. Statistical analysis was aimed at developing multivariable risk-adjustment models Results: Many factors correlated with suboptimal RD in multivariate analysis: large TE (OR: 5.48; 95%CI: 2.53–12.85), low SCS (OR: 38.44; 95% CI: 15.81–115.87) presence of ascites (OR: 3.22; 95%CI:1.34–9.06) and age (OR: 1.02; 95%CI:1.00–1.04. Low performance status (ASA 3,4 vs 1,2; HR:1.29; 95%CI: 1.04–1.61), large TE (HR:1.76; 95%CI: 1.41–2.21), and RD >1cm (HR:1.88; 95%CI: 1.27–2.51) independently correlated with decreased OS. High SCS and low RD were associated with improved survival, especially in patients with large TE. A very high risk group could be identified (N=38, 6.6%) by combing the following factors (large TE or stage IV, poor performance and nutritional status, ascites). In this group high SCS to achieve low RD was associated with perioperative morbidity of 63.6% with no survival benefit as opposed to lower SCS. The importance of each factor was applied to each patient to predict the rates (expected=E) of RD and OS for each center’s cohort and compared to the actual (observed=O) rate of outcome to arrive at O/E ratios. O/E ratios were not statistically different between institutions indicating comparable quality of care when risk-adjusted Conclusions: Improvement in surgical outcomes in AOC requires accurate, risk-adjusted measurement of outcomes. SCS and low RD remain independent predictors of OS. The benefits of more complex surgery appear to outweigh the added morbidity in most subgroups. Efforts to improve peri-operative care and further selection criteria for aggressive procedures should be the objective of future large prospective studies No significant financial relationships to disclose.
Multicenter, prospective study of radiotherapy without surgery after AC followed by weekly paclitaxel for patients with inflammatory breast cancer: SBCCSG-04 study
Authors: T. Tabei, K. Sato, K. Inoue, S. Nakano, T. Kai, K. Futsuhara, S. Yamashita, T. Saito, T. Kuroda, K. Suemasu
Journal: Journal of Clinical Oncology (2006)

10783 Background: Inflammatory breast cancer (IBC) is a rare and aggressive disease with a dismal outcome. It is still an open debate whether surgery is beneficial for patients with IBC. This study was conducted to evaluate treatment results when patients were treated by chemotherapy and radiotherapy (CRT) alone. Methods: 52 pts with nonmetastatic IBC were enrolled for a prospective registration trial from 9/01–11/04. A diagnosis required the presence of erythema, ridging, or peau d’orange, with or without dermal lymphatic invasion (DLI). All patients were invited to participate for an experimental protocol; 4 cycles of AC and 12 cycles of weekly paclitaxel (80 mg/m 2 ) followed by radiotherapy. In patients who did not agree to the protocol, the decision about treatment was left to the patients/investigators. The primary endpoint was distant-disease-free survival, and the further endpoints were locoregional relapse (LR) and overall survival. Results: The mean follow-up was 25.7 months. 24 pts (46.2%) were planned for the protocol, but one pt (4%) was receipt surgery. Otherwise, 18 (64%) out of 28 pts have accepted mastectomy. The 2-year distant-disease-free, LR, and overall survival in patients treated with and without the protocol was 35.2 vs 61.0% (HR = 2.4, 1.1–5.3) and 55.2 vs 83.6% (HR = 2.9, 1.1–7.8), respectively. Surgery was not associated with the risk of LR (p = 0.48). There was marginally worse prognosis in patients with DLI. Conclusions: There was a limitation because this comparison had not been conducted a randomized fashion. However, CRT alone would be a feasible treatment schedule for a moderate percentage of patients with IBC. No significant financial relationships to disclose.
Platinum-based chemotherapy in triple-negative breast cancer.
Authors: C. M. Villarreal-Garza, M. Clemons, F. Kassam, K. Enright, S. Verma, J. A. Myers, R. A. Dent
Journal: Journal of Clinical Oncology (2011)

1090 Background: There is increasing evidence that DNA repair defects characteristic of BRCA1-related cancers and triple negative breast cancer (TNBC) confer sensitivity to certain chemotherapeutic agents, such as platinums. However, prospective and retrospective studies comparing the efficacy of these agents versus conventional treatment in TNBC are lacking. The aim of this study was to evaluate the efficacy of platinum-based chemotherapy (PBC) in metastatic TNBC in terms of median duration of treatment and overall-survival (OS) and compare it to patients treated with conventional chemotherapy. Methods: We performed a retrospective chart review of patients with metastatic TNBC who received PBC from January 2007 to June 2010 treated at the Sunnybrook Odette Cancer Center. A case-control study was designed, with 3 controls per case matched by age, comprising metastatic TNBC treated with conventional agents. Results: A total of 116 patients were analyzed: 29 treated with PBC and 87 managed with conventional treatment. Median age at diagnosis was 47 years and distant disease-free interval was 27 months (m) for both groups. Patients treated with PBC had more sites of disease (100% vs. 70%, p<0.0001) and a worse performance status (ECOG 2 21% vs. 6%, p=0.034), respectively. Of the 29 patients treated with PBC, 79% received a combination regimen, most commonly weekly cisplatin and gemcitabine in 62% of patients. The median number of cycles delivered was 4 (2-11). 31% received PBC as first-line treatment, 35% as second-line, 28% as third-line and 7% as fifth-line. Only 2 patients discontinued PBC secondary to toxicity. The median time on treatment in first, second and third-line therapy was longer for the PBC group (5 vs. 2 m, p=0.225; 3 vs. 2 m, p=0.063; and 4 vs. 1 m, p=0.009). Patients treated with PBC had a longer OS compared to those managed conventionally (18 vs. 13 m, p=0.025). Conclusions: PBC appears to improve clinical outcomes in patients with metastatic TNBC compared to those treated with conventional chemotherapy regimens. Although this is a retrospective study with its obvious limitations, it adds to the growing body of literature, suggesting the benefit of PBC in TNBC. Prospective trials are needed to confirm this benefit.
Abstract 17144: Assessment of Tissue Heating During Cardiac Radiofrequency Ablation Using Referenceless MRI Thermography
Authors: Aravindan Kolandaivelu, Menekem Zviman, Valeria Sena-Weltin, Henry Halperin
Journal: Circulation (2011)

Introduction: Imaging tissue heating during RF ablation may permit more accurate placement and titration of ablation lesions. Standard proton resonance frequency shift MRI thermography, however, is limited by sensitivity to physiologic motion and scanner phase drift between acquisition of ablation and reference pre-heating images. The aim of this study is to assess the feasibility of referenceless MRI thermography which addresses this limitation by eliminating need for a separate pre-heating image but has not yet been applied to cardiac ablation. Methods: An MRI compatible copper electrode catheter was inserted into the left ventricle in 6 dogs. Gradient recalled echo images were acquired while applying RF power in 3W increments until high impedance was reached. Gross pathology was obtained. The pre-heating image was estimated from the ablation image phase component (A) by unwrapping phase (B), masking the catheter tip region where heating was expected (C), and extrapolating phase from unmasked regions of the heart using a fourth order polynomial fit (D). Thermography images were then computed using standard methods (E). Thermography lesion extent was defined by tissue temperature above 50°C. Electrode artifact was defined by darkened myocardium adjacent to the catheter tip on the magnitude component of the ablation image. Results: Transmural lesion extent by referenceless MR thermography was within 20% of that obtained by pathology (inset F) in the four cases where the electrode artifact transmurality was less than 25%. However, thermography and pathology lesion extent differed by over 60% in the two cases where electrode artifact transmurality was greater than 40%. Conclusion: Referenceless MR thermography of cardiac RF ablation is possible and may permit more practical MR thermography monitoring of cardiac ablation. Reducing electrode artifact by using lower magnetic susceptibility materials appears required for more reliable temperature assessment.
Specific gene expression profiles and unique chromosomal abnormalities are associated with regressing tumors among infants with disseminated neuroblastoma
Authors: C. Lavarino, N. Cheung, C. de Torres, G. Domenech, I. Garcia, M. Alaminos, J. Ríos, W. Gerald, B. Kushner, M. LaQuaglia, J. Mora
Journal: Journal of Clinical Oncology (2007)

9501 Background: Among human cancers, neuroblastoma (NB) has the highest incidence of spontaneous remission, especially among the subgroup of stage 4s NB affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical, since it is the basis for therapeutic decisions. The identification of biological markers that allow a precise distinction of these NB subgroups will aid accurate classification. Methods: Thirty-seven infants with NB were treated at MSKCC from 1987 to 2000. Ten stage 4s and 19 stage 4 were evaluated by allelic and gene expression analyses. Results: All stage 4s patients underwent spontaneous remission while only 69% of newly diagnosed, previously untreated stage 4 patients survived despite combined modality therapy. Among stage 4 tumors, 19/19 were near-diploid/tetraploid, 8/19 MYCN amplified, 50% had LOH at 1p36, 43% had LOH at 1p34-p31 and/or 14q and 37% had LOH at 11q and/or 1p22. Among stage 4s tumors, 7/8 were near-triploid, none MYCN-amplified and LOH was restricted to 11q. Gene expression profiling identified 233 differentially expressed genes between stage 4 and 4s tumors. 25% of these genes with increased expression in stage 4s NB mapped to 1pter-p13, with transcription level correlated with LOH and ploidy. Conclusions: These findings suggest that differential expression of subsets of genes located at specific chromosomal regions play a significant role in the biology of disseminated NB. Besides offering a biological definition of stage 4s, these expression profiles may provide new insights in the genetic control of spontaneous remission in neuroblastoma. No significant financial relationships to disclose.
Dose-response in the treatment of breast cancer: a critical review.
Authors: I C Henderson, D F Hayes, R Gelman
Journal: Journal of Clinical Oncology (1988)

In animal tumor models the dose-response curve for cytotoxic agents, especially cyclophosphamide, may be steep, but the slope and shape of this curve depends not only on the drug used but on the schedule of drug administration, the specific tumor type, tumor cell kinetics, and tumor mass. It might be anticipated from these studies that the human tumors most sensitive to dose effects would be leukemia, lymphoma, small-cell carcinoma of the lung, and testicular tumors rather than the low growth fraction, relatively less responsive tumors such as breast cancer. However, the clinical evidence for a steep dose-response curve in any tumor type is limited. For breast cancer such evidence is largely retrospective or derived from uncontrolled trials. The data available from randomized trials makes it seem unlikely that small, or even moderate, reductions in drug dose for nontrivial reasons will compromise the survival of patients with either early or metastatic disease. In spite of promising data from small trials, there is, as yet, inadequate evidence to justify the use of very-high-dose therapy and autologous marrow transplant outside the setting of a well-designed clinical trial. The value of high-dose therapy, intensive dose rate, and cumulative drug dose should each be studied in randomized controlled trials.
Predictors of bone mineral density in pediatric cancer survivors
Authors: T. L. Miller, S. Lipsitz, C. French, A. Hinkle, L. Constine, A. Kozlowski, C. Proukou, S. E. Lipshultz
Journal: Journal of Clinical Oncology (2005)

8518 Introduction: Bone mineral density (BMD) of survivors of childhood cancer has been described previously with variable results. Methods: We prospectively studied BMD [total, spine, leg] (using DXA) in a cohort of survivors of childhood cancer greater than 5 years from diagnosis and sibling controls. We simultaneously evaluated the following measures at the time of BMD testing: age, race, gender, years since dx, age at dx, chemotherapy (type), radiation (type), body mass index (BMI), dietary intake (total calories, vitamin D, calcium; expressed as % RDA), estrogen, testosterone, LH, FSH, fasting insulin, IGF-1, T4, and TSH. Results: 158 cancer survivors and 60 sibling controls were evaluated. Siblings were significantly (p=0.005) younger than the survivors (16.2 yrs [se=8.0] vs 19.8 yrs [se=8.5] with an equal distribution of males and females. Survivors were a mean of 11.7 yrs since dx. 42% had past dx of leukemia. In an unadjusted analysis, there were no differences in BMI or BMD between groups, although FSH was higher (p=0.04) and IGF-1 (p=0.0005) was lower in the cancer survivors. After adjusting for age, gender, and BMI, girl cancer survivors had lower total, spine, and leg BMD, whereas there were no differences in boys. Multivariate models to ascertain predictors of BMD were developed for both boy and girl cancer survivors. For boys, BMI (estimate=.012; p<0.0001), age (.006, p=0.003), cranial radiation (-.08, p=.0003), and testosterone (.0003, p<.0001) were independently associated with total BMD. For girls, BMI (estimate=.0002; p=0.03), age (.009, p<.0001), spinal radiation (-.17, p=.10), sarcoma diagnosis (.102, p=.025) and IGF-1 (.0003, p=.04) were independently associated with total BMD. Total caloric, calcium, and vitamin D intake did not predict BMD. Conclusion: Bone mineral density is reduced in females survivors of childhood cancer compared with sibling controls. BMD was higher in males who were older, had higher BMI and testosterone levels and who had not received cranial radiation. BMD was higher in older females with higher BMI and IGF-1 levels, prior dx of sarcoma and no spinal irradiation. The diagnosis of cancer and its therapy appear to affect BMD. No significant financial relationships to disclose.
Technique for training schizophrenic patients in illness self- management: a controlled trial
Authors: T A Eckman, W C Wirshing, S R Marder, R P Liberman, K Johnston-Cronk, K Zimmermann, J Mintz
Journal: American Journal of Psychiatry (1992)

To determine whether schizophrenic outpatients receiving low-dose neuroleptic therapy could learn and retain complex information and skills related to self-management of their illness, a novel technique of teaching, using cognitive and behavioral methods, was designed to compensate for the patients' learning disabilities.The subjects were 41 patients with DSM-III-R schizophrenia who were receiving constant maintenance neuroleptic drug therapy. They were randomly assigned to structured, modularized skills training or to supportive group psychotherapy.The patients who received skills training made significant gains in each of the areas taught, while those participating in group therapy did not. The skills learned during training were retained without significant erosion over a 1-year follow-up period.The effectiveness of modularized teaching of illness self-management skills to schizophrenic patients appears to be largely independent of baseline psychology and symptom improvement. Such an approach is useful for overcoming or compensating for the enduring cognitive and information processing deficits commonly found in schizophrenia.
Prediction of pathologic response of colorectal liver metastases (CRLM) to transcatheter hepatic therapy with irinotecan-eluting beads by hepatic activation of irinotecan.
Authors: Robert Peter Jones, Paul Sutton, Anahi Santoyo-Castelazo, Hassan Zakria Malik, Stephen W Fenwick, Monica Terlizzo, Graeme John Poston, Neil Kitteringham
Journal: Journal of Clinical Oncology (2013)

438 Background: For patients with CRLM, good pathologic response to neoadjuvant chemotherapy is associated with improved overall survival. However, systemic therapy can increase postoperative morbidity and mortality. DEBIRI gives sustained delivery of drug directly to tumor, maximising response and reducing systemic exposure. Predictive markers of response would allow selection of patients most likely to benefit. This study assessed drug metabolism within normal hepatic parenchyma as a predictor of pathologic response of CRLM to DEBIRI. Methods: Patients with resectable CRLM received single targeted DEBIRI (up to 200mg) 1 month pre-hepatectomy. Hepatic parenchyma was harvested at resection. Parenchymal drug metabolism and protein expression were characterised with a novel LC-MS/MS assay and western blot, and correlated with pathologic tumour response. Results: Ten patients assessed. Median residual tumour 30% (range 10-50%), necrosis 40% (range 40-60%) and fibrosis 20% (range 10-40%). Microsomal formation of SN-38 was 0.52-2.19 nmol/mg/min (mean 1.02), SN-38G 0.30-0.59 nmol/mg/min (mean 0.43), APC 0.1-0.24 nmol/mg/min (mean 0.18). There was a negative correlation between SN-38 production and degree of SN-38 glucuronidation (r 2 =0.42, p=0.04), with no difference between heterozygous/wild-type UGT1A1*28 patients. SN-38 production demonstrated a strong correlation with CES-2 expression (r 2 =0.96, p&lt;0.001), with a strong correlation between the glucuronidation of SN-38 and UGT1A1 expression (r2=0.76, p=0.01). A moderate correlation between microsomal SN-38 production and degree of tumour necrosis was obtained (r 2 =0.30, p=0.07). A highly significant correlation between microsomal SN-38 production and degree of tumour fibrosis was observed (r 2 =0.54, p=0.01). Conclusions: Metabolism of irinotecan varies widely. Production of the active metabolite SN-38 is directly mediated by CES-2, and hepatic production of SN38 predicts degree of tumour fibrosis after DEBIRI. Metabolic profiling may offer a novel predictor of response to DEBIRI.
Management of hypocalcemic effects of WR2721 administered on a daily times five schedule with cisplatin and radiation therapy. The New York Gynecologic Oncology Group.
Authors: S Wadler, H Haynes, J J Beitler, G Goldberg, J F Holland, H Hochster, H Bruckner, J Mandeli, H Smith, C Runowicz
Journal: Journal of Clinical Oncology (1993)

To determine the effects of the chemoprotective agent, WR2721, administered on a daily x 5 schedule with cisplatin and radiation therapy, on calcium and parathyroid hormone (PTH) levels.Twenty women with cervical cancer were enrolled in a clinical trial to determine the maximal safe dose of WR2721 plus radiation therapy and cisplatin on a novel daily x 5 schedule. Detailed studies of the effects of WR2721 on calcium and PTH levels were initiated after a patient developed symptomatic hypocalcemia.Treatment with WR2721 resulted in a rapid decline in serum PTH levels within 4 hours, which fell below the lower limits of normal at 24 hours, then returned to within normal limits at 48 hours. In contrast, serum levels of ionized calcium were not affected acutely, and declined by only 7% within 24 hours. However, this small decrease persisted for the 5 days of treatment. Hypocalcemic effects were successfully managed with oral calcium carbonate and calcitriol supplements. In one patient, particularly sensitive to the effects of WR2721, serum levels of ionized calcium decreased to less than 3.0 mg/dL despite oral calcium supplements.The effects of WR2721 on serum ionized calcium levels are mediated by direct inhibition of PTH activity; other effects such as inhibition of renal tubular calcium reabsorption cannot be excluded. We recommend that patients treated with WR2721, cisplatin, and radiation therapy receive routine oral calcium and calcitriol supplementation and that serum ionized calcium levels be monitored frequently.