tbuckley/cabot-search huggingface dataset:
Value of thoracic multidisciplinary clinic (TMDC) in determining appropriate treatment of stage III non-small cell lung cancer (NSCLC).
Authors: Eliot L Friedman, Michael F Szwerc, Robert Kruklitis, Michael J Weiss
Journal: Journal of Clinical Oncology (2013)

82 Background: Treatment of stage III NSCLC involves surgery, radiation therapy and chemotherapy. Treatment depends on the size and location of the primary tumor and lymph nodes as well as clinical status of the patient. Evaluation of these patients should take place in a multidisciplinary clinic, where treating physicians and pulmonary medicine provide a unified treatment plan. Methods: All patients with Stage III NSCLC seen at the Lehigh Valley Health Network (LVHN) between March of 2010 and March of 2012 were analyzed retrospectively. We compared initial treatment of out-patients seen in our TMDC with those out-patients seen outside the TMDC. Results: Thirty-five patients were seen in TMDC (34 treated at LVHN) and 44 patients were seen outside TMDC (34 treated at LVHN). Eleven patients were treated elsewhere or were not treatable. Of patients with stage III NSCLC, 37.5% were seen in TMDC year 1 (March 2010 – March 2011) compared to 61% of patients year 2 (March 2011 – March 2012) (p = 0.05). Patients were seen by physicians from at least two specialties 100% of the time when seen in TMDC, but only 64.7% of the time when seen outside TMDC (p &lt; 0.001). Mediastinal staging (EBUS or mediastinoscopy) was performed more frequently in patients seen in TMDC; 58.9% compared to 23.5% outside TMDC (p = 0.009). The LVHN clinical pathway for stage III NSCLC recommends initial therapy with concomitant chemoradiation, either in the neo-adjuvant setting or as definitive treatment. Eighty-eight percent of patients seen in TMDC followed our clinical pathway while 46% of patients seen outside TMDC conformed to the clinical pathway (p &lt; 0.001). The time from first contact with a treating physician to initiation of treatment was reduced by almost 30% (29.03 days outside TMDC; 20.62 days at TMDC). Conclusions: All patients with stage III NSCLC should be seen in a multidisciplinary setting. At LVHN we saw an increase in these patients being referred to our TMDC over time. These patients were more likely to have mediastinal staging and enjoyed quicker initiation of their therapy. They were more likely to have at least two physicians involved in their initial treatment plan and were more likely to conform to our clinical pathways.
Phase I drug-interaction study of effects of calcium and magnesium infusions on oxaliplatin pharmacokinetics and acute neurotoxicity in colorectal cancer patients.
Authors: Catherine HyeWon Han, Prashannata Khwaounjoo, Dean H. Kilfoyle, Andrew Graham Hill, Mark James McKeage
Journal: Journal of Clinical Oncology (2014)

578 Background: Calcium and magnesium (Ca/Mg) infusions have been suggested as an effective intervention for preventing oxaliplatin-induced neurotoxicity, but the effects of Ca/Mg infusions on oxaliplatin pharmacokinetics, motor nerve hyperexcitability, and acute neurotoxicity symptoms are unclear. Methods: In this double-blind crossover study, colorectal cancer patients undergoing oxaliplatin-based chemotherapy were randomised to receive Ca/Mg (1g Ca Gluconate plus 1g MgSO 4 ) on cycle 1 and placebo (vehicle alone) on cycle 2, or to receive the same treatments in the opposite sequence. Study endpoints included plasma pharmacokinetics of intact oxaliplatin and free platinum; electromyography (EMG) detection of abnormal spontaneous high-frequency motor unit action potential discharges; and patient-reported acute neurotoxicity symptoms and their preferred study treatment for reducing these symptoms. Results: The planned accrual target was achieved. Nineteen of 20 enrolled patients completed the study. Plasma pharmacokinetics of intact oxaliplatin and free platinum were similar when oxaliplatin was given with Ca/Mg or placebo (ratio of geometric means of AUC 0-t with Ca/Mg or placebo: intact oxaliplatin, 0.95 (90% CI, 0.90 – 1.01); free platinum, 0.99 (90% CI, 0.94 – 1.05)). EMG motor nerve hyperexcitability scores were similar with Ca/Mg and placebo (mean difference in EMG score between Ca/Mg and placebo: -0.3 (95% CI, -2.2 – 1.6)). Patient-reported acute neurotoxicity symptoms were similar in frequency with Ca/Mg and placebo. For reducing neurotoxic symptoms, fewer patients preferred Ca/Mg than placebo or neither treatment (26% versus 74%; p &lt; 0.01). Conclusions: Ca/Mg infusions do not alter the clinical pharmacokinetics of oxaliplatin and do not seem to reduce its acute neurotoxicity. Clinical trial information: ACTRN12611000738921.
PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors
Authors: Harriet M. Kluger, Christopher R. Zito, Gabriela Turcu, Marina K. Baine, Hongyi Zhang, Adebowale Adeniran, Mario Sznol, David L. Rimm, Yuval Kluger, Lieping Chen, Justine V. Cohen, Lucia B. Jilaveanu
Journal: Clinical Cancer Research (2017)

Purpose: With recent approval of inhibitors of PD-1 in melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma, extensive efforts are under way to develop biomarkers predictive of response. PD-L1 expression has been most widely studied, and is more predictive in NSCLC than renal cell carcinoma or melanoma. We therefore studied differences in expression patterns across tumor types.Experimental Design: We used tissue microarrays with tumors from NSCLC, renal cell carcinoma, or melanoma and a panel of cell lines to study differences between tumor types. Predictive studies were conducted on samples from 65 melanoma patients treated with PD-1 inhibitors alone or with CTLA-4 inhibitors, characterized for outcome. PD-L1 expression was studied by quantitative immunofluorescence using two well-validated antibodies.Results: PD-L1 expression was higher in NSCLC specimens than renal cell carcinoma, and lowest in melanoma (P = 0.001), and this finding was confirmed in a panel of cell lines. In melanoma tumors, PD-L1 was expressed either on tumor cells or immune-infiltrating cells. The association between PD-L1 expression in immune-infiltrating cells and progression-free or overall-survival in melanoma patients treated with ipilimumab and nivolumab was stronger than PD-L1 expression in tumor cells, and remained significant on multivariable analysis.Conclusions: PD-L1 expression in melanoma tumor cells is lower than NSCLC or renal cell carcinoma cells. The higher response rate in melanoma patients treated with PD-1 inhibitors is likely related to PD-L1 in tumor-associated inflammatory cells. Further studies are warranted to validate the predictive role of inflammatory cell PD-L1 expression in melanoma and determine its biological significance. Clin Cancer Res; 23(15); 4270-9. ©2017 AACR.
The conversion ratio from intravenous (IV) hydromorphone to oral (PO) opioids in patients with cancer.
Authors: Akhila Sunkepally Reddy, Sara Dost, Marieberta Vidal, Saneese Stephen, Karen Baumgartner, Jimin Wu, Diane D Liu, Sriram Yennu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

197 Background: Inpatients with cancer frequently undergo conversions from IV to PO hydromorphone (HM) or opioid rotation (OR) from IV HM to another PO opioid prior to discharge. Currently used conversion ratios (CR) between IV and PO HM range from 2-5 and opioid rotation ratios (ORR) between IV HM and oral morphine equivalent daily dose (MEDD) range from 10-20. This large variation in ratios may lead to uncontrolled pain or overdosing. Our aim was to determine the accurate CR from IV to PO HM and ORR from IV HM to PO morphine and oxycodone (measured as MEDD). Methods: We reviewed records of 4745 consecutive inpatient palliative care consults in our institute during 2010-14 for patients who underwent conversion from IV to PO HM or OR from IV HM to PO morphine or oxycodone. Patient characteristics, symptoms and opioid doses were determined in patients successfully discharged on oral opioids without readmission within 1 week. Linear regression analysis was used to estimate the CR or ORR between the 24 hour IV HM mg dose prior to conversion to PO and the oral opioid mg dose used in the 24 hours prior to discharge. Results: Among 394 eligible patients on IV HM, 147 underwent conversion to PO HM and 247 underwent OR to oral morphine (163) or oxycodone (84). Mean age was 54 years, 39% were male, and 95% had advanced cancer. Median time between conversion to PO and discharge was 2 days. In 147 patients the median CR (IQR) from IV to PO HM was 2.5 (2.1-2.7) and correlation of IV to PO dose of HM was .95 (P &lt; .0001). The median CR was 2.5 in patients receiving &lt; 30mg of IV HM/day and 2.1 in patients receiving ≥ 30mg of HM/day (P = .004). In 247 patients the median ORR (IQR) from IV HM to MEDD was 11.5 (10-13) and correlation of IV HM to MEDD was .93 (P &lt; .0001). The median ORR was 11.5 in patients receiving &lt; 30mg of IV HM/day and 9.9 in patients receiving ≥ 30mg of HM/day (P = .0004). ORR from IV HM to MEDDs obtained from morphine (11) and oxycodone (12.1) were significantly different (P = .0023). The CR and ORR were not significantly impacted by other variables. Conclusions: The median CR from IV to PO HM is 2.5 and ORR from IV HM to MEDD is 11.5. This implies that 1 mg IV HM is equivalent to 2.5 mg PO HM and 11.5 mg MEDD. HM may cause hyperalgesia at doses ≥ 30 mg/day and thereby requires a lower ORR to other opioids.
MicroRNA-21 as an indicator of aggressive phenotype in breast cancer.
Authors: A. Ozgun, B. Karagoz, O. Bilgi, T. Tuncel, E. G. Kandemir
Journal: Journal of Clinical Oncology (2011)

e11010 Background: MicroRNAs (miRNAs) are a new class of non-protein-coding, endogenous, small RNAs. They have clinical significance because of their relationship to cancer pathogenesis. miRNAs act as an oncogene or a tumour supressor gene in cancer pathogenesis. MicroRNA-21 (miR-21) shows the highest expression level and acts as an oncogene in breast cancer. The purposes of this study are to measure miR-21 expression in early-stage breast cancer and to analyze its association with clinicopathologic features. Methods: Formalin-Fixed, Paraffin-Embedded (FFPE) tissue samples were collected from 15 patients who underwent surgery for primary breast cancer. The expression level of miR-21 was measured by the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis in the tumor tissue and normal breast tissue. Levels of miR-21 expression in terms of disease stage, tumor size, nodal involvement, hormone receptor status and HER2 status were compared. Results: miR-21 expression was detected in all tumor samples and the level of miR-21 expression was higher than the normal breast tissue samples (p=0,001). There were no significant differences among miR-21 expression levels in terms of tumor size and hormone receptor status, but significant differences were observed in terms of nodal involvement (p=0.037), disease stage (p=0.005) and HER2 status (p=0.014). The expression level of miR-21 was higher in patients with four or more nodal involvement, patients with Stage III and HER2-positive patients than in patients with three or less nodal involvement, patients with Stage I or II and HER2-negative patients, respectively. Conclusions: These findings suggest that microRNA-21 is expressed in breast cancer and the high expression level of miR-21 is associated with more nodal involvement, more advanced disease stage and HER2-positive status. These results demonstrate that high expression level of miR-21 indicates a more aggressive phenotype of breast cancer. miR-21 may play an important role in breast cancer progression and therefore it may be a novel therapeutic target for the treatment of breast cancer.
A phase II trial of dasatinib in subjects with hormone-refractory prostate cancer previously treated with chemotherapy.
Authors: P. Twardowski, C. Chen, A. S. Kraft, G. S. Chatta, E. Alexson, M. Mitsuhashi, W. Ye, M. Lilly
Journal: Journal of Clinical Oncology (2011)

4575 Background: The efficacy of therapies for prostate cancer following failure of androgen deprivation and docetaxel is limited. SRC dysregulation may be important in prostate cancer progression. Dasatinib (DAS) is an inhibitor of tyrosine kinases including the SRC family. Methods: Patients with metastatic castration-resistant prostate cancer (CRPC) treated with one prior chemotherapy regimen were enrolled. Starting dose of DAS was 70 mg BID. It was amended to 100 mg/day after 6 patients were treated. Response rate (RR) and progression free survival (PFS) were assessed in a 2-stage design (21+20). A maximum of 41 patients were to be accrued to rule out a null hypothesized positive effect (PR, CR and SD) of 5% versus alternative of positive effect of 20% with α=0.05 and β=0.1. Correlative studies on blood, urine specimens were performed. Results: 38 subjects were enrolled, 26 were evaluable for response or toxicity. Median duration of therapy was 55 days (6-284 days). 12 patients (46%) had dose reduction or treatment delay. One PSA PR (3.8% RR, 95% CI: 0.1%-19.6%) was seen. This patient remained on treatment for 284 days. One patient (3.8%) had stable disease for more than 6 months. Median time to treatment failure was 29 days (95% CI: 28-37 days). 31% of patients discontinued treatment without having progression of disease. Attributable grade 3 and 4 toxicities included: pleural and pericardial effusions (23%), fatigue (19%), elevated lipase (12%), dyspnea (8%), hyponatremia (8%), diarrhea (8%), GI bleed (8%), anemia (4%), venous thrombosis (4%). Most subjects showed decline in PHA-stimulated expression of GMCSF, CD40L, GZMB and IL-2 cytokines in PBMNCs following start of DAS, consistent with its biologic effect. Decrease in serum IL-6 of ≥50% was noted within 28 days of therapy in patients with PR and SD. Conclusions: The initial DAS dose was poorly tolerated in these advanced CRPC subjects. Tolerability was improved by reduction in starting dose to 100mg/d. Activity of DAS in chemo-pretreated CRPC patients is limited, but the observation of cases with prolonged clinical benefit warrants further investigation of this agent in the context of molecular profiling and appropriate patient selection.
IPH2101, a Novel Anti-Inhibitory KIR Monoclonal Antibody for Multiple Myeloma: Interm Phase 1 Trial Results and Correlative Biologic and Safety Data
Authors: Don M Benson, Courtney E Bakan, Swaminathan Padmanaban, Rafat Abonour, Attaya Suvannasankha, Sundar Jagannath, Ajai Chari, David Clever, Chidimma Kalu, Shauna Collins, Yousef Alghothani, Craig C. Hofmeister, Yvonne Efebera, Stephane Blanchet, Michael A. Caligiuri, Sherif Farag
Journal: Blood (2010)
Impact of smoking on anatomical distribution and survival in women with lung cancer
Authors: A. E. Sahmoun, A. K. Ganti, A. W. Panwalkar, K. Tendulkar, A. Potti
Journal: Journal of Clinical Oncology (2005)

9704 Background: Smoking is the main cause of lung cancer. Recent studies have indicated that female smokers may be more susceptible to lung cancer than male smokers. 75–80% of female lung cancer related deaths are among smokers. While the carcinogenic potential of tobacco smoking is clear, important clinical and prognostic features of smoking related lung cancer in women are yet undetermined. Methods: We conducted a retrospective review of medical charts of women diagnosed with lung cancer. Clinical data related to the diagnosis and treatment of lung cancer was reviewed. Statistics were calculated with χ2 or Fisher’s exact tests, Kaplan-Meier estimates with log-rank tests, and Cox proportional-hazards models. Results: Four hundred and twenty-eight women with biopsy-proven lung carcinoma and a documented history of smoking were eligible for this study. The median age was 66 years (range: 31–91 years). Three hundred and thirteen (73%) were non-small cell lung cancer (NSCLC) and 115(27%) were small-cell lung cancer (SCLC). Adenocarcinoma and SCLC were more common in the upper lobe 154(49%) and 47(41%) respectively, (p<0.001). Adenocarcinoma 73(25%) was significantly more common in the upper lobe than squamous cell carcinoma 51(17%) (p=0.004). Radiotherapy alone 90(29%) was the preferred first line of treatment in NSCLC while the combination of chemotherapy and radiotherapy 63(55%) was mostly used in SCLC. Fifty-four (47%) of the women with SCLC relapsed compared with only 103(33%) with NSCLC (p=0.007). Survival was no different in smoking women with NSCLC compared to SCLC (65 months vs. 80 months; log-rank p=0.3). The multivariable Cox model showed an adjusted HR of 0.27 (95% CI: 0.11–0.67) for cisplatin relative to carboplatin-based therapy at diagnosis in NSCLC. We found no impact of anatomical distribution or pulmonary location on the prognosis. Conclusions: In women smokers, adenocarcinoma is the most common subtype of NSCLC seen. The upper lobes were the most common site for adenocarcinoma and SCLC. Cisplatin-based therapy is associated with a better survival than carboplatin-based therapy in women with NSCLC. No significant financial relationships to disclose.
Long-term collaboration for building sustainable palliative care in Belarus.
Authors: Sarah Slater, Kathleen Doyle
Journal: Journal of Clinical Oncology (2015)

142 Background: The WHO and the Worldwide Palliative Care Alliance have published findings that only 10% of the 20.4 million people who need palliative care currently receive it. A major barrier to meeting that need is insufficient education of healthcare workers in palliative care. Over the last decade, palliative care has attracted significant interest from the government of Belarus, with the first adult hospice founded in 2005 and introduced palliative care into the National Healthcare Law in 2013. However, the country faces a shortage of healthcare providers trained in palliative care. We report on the experience of developing and implementing a palliative care curriculum in Belarus. Methods: We first conducted a needs assessment that examined physician knowledge of and attitudes toward palliative care, the legal status of palliative care, drug availability, and other topics. We utilized past in-country experience, a literature review, a questionnaire, and interviews with Belarusian colleagues. Based on the needs assessment, we developed, modified, and translated a 25-lecture curriculum that was comprehensive, at an adequate difficulty level, and culturally appropriate. A team of four clinicians taught the curriculum in Belarus over to an audience of physicians, and healthcare administrators. Results: The course was well-received—participants were satisfied, reported a better understanding of palliative care, and improved their skills and confidence in managing symptoms and discussing prognosis. Conclusions: We have continued our collaboration with our Belarusian colleagues. New government policies and have passed which promote palliative care. We subsequently held a web-based teleconference with members of the Ministry of Health as well has medical education administrators in Belarus to discuss the structure of palliative care programs in the United States and our model of palliative care education. A second in-person palliative care education workshop for both physicians and nurses is being planned for the fall of 2015. We hope that our experience provides encouragement and resources for the continued promotion of palliative care education and development worldwide.
Evaluation of response after chemoradiation for rectal cancer as a predictive factor for the benefit of adjuvant chemotherapy: A pooled analysis of 2,724 individual patients.
Authors: G. L. Beets, M. Maas, P. J. Nelemans, V. Valentini, C. H. Crane, C. Capirci, C. Roedel, L. Kuo, J. Garcia-Aguilar, R. Glynne-Jones
Journal: Journal of Clinical Oncology (2011)

361 Background: Neoadjuvant chemoradiation (CRT) for rectal cancer increasingly results in pathologic response. It has been suggested that patients with different degrees of response might not have the same benefit of adjuvant chemotherapy. The aim was to determine whether patients with a pathologic complete response (pCR), ypT1-2 or ypT3-4 tumor after CRT for rectal cancer have different benefits of adjuvant chemotherapy for disease-free survival. Methods: Authors from studies evaluating different degrees of response to CRT were contacted to share individual patient data. The collected individual patient data were pooled into one dataset. To evaluate the effect of adjuvant chemotherapy on disease-free survival multivariate analyses according to the Cox proportional hazards model were performed. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated for 3 subgroups: patients with pCR(ypT0N0), ypT1-2 tumor and ypT3-4 tumor after CRT. To determine benefit of adjuvant chemo for different pathologic N-stages we performed subgroup analyses. Results: 2,724 patients were included. 811 had pCR (28%), 863 had ypT1-2 (30%) and 1050 had ypT3-4 (37%). Median follow-up was 50 months (range 0-277). 41% underwent adjuvant chemotherapy, which consisted mostly of 5-FU based chemotherapy. The HR with 95%CI for disease-free survival for adjuvant chemotherapy was 0.94 (0.50-1.78) for patients with pCR, 0.61 (0.40-0.92) for patients with ypT1-2 tumors and 0.97 (0.75-1.25) for patients with ypT3-4 tumors. ypT1-2N0 patients benefited most from adjuvant chemo: HR 0.45 (0.27-0.75) vs. 0.79 (0.31-1.95) for patients with ypT1-2N+. For ypT3-4 patients pN-stage did not alter benefit of adjuvant chemo. Conclusions: Patients with pCR or ypT3-4 residual tumor after CRT do not seem to benefit from adjuvant chemo. This might be due to the already good prognosis of patients with pCR and less responsiveness to 5-FU based chemotherapy in the poor responders (the ypT3-4 tumors). Possibly adjuvant chemotherapy can be omitted or adapted for these patients. Patients with ypT1-2N0 benefit most from adjuvant chemo. No significant financial relationships to disclose.