tbuckley/cabot-search huggingface dataset:
Effects of interstitial laser photocoagulation on normal lung parenchyma
Authors: D. I. Fielding, G. Buonaccorsi, A. Hanby, M. Hetzel, S. G. Bown
Journal: Thorax (1996)

Poor lung function can preclude surgical cure of non small cell lung cancer and post radiation fibrosis limits the role of radiotherapy. An alternative treatment in patients unfit for surgery may be the use of interstitial laser photocoagulation (ILP).Laser fibres are passed percutaneously into tumours as for a fine needle biopsy and necrosis is produced by gentle localised heating from a low power laser.As tumour ablation will require treatment of some normal adjacent tissue we investigated the effects of ILP on normal lung parenchyma. In Wistar rats a 0.4 mm fibre was inserted percutaneously under general anaesthetic into the the left lung. All rats had fluoroscopic screening immediately after ILP to detect pneumothorax. Lesions were ellipsoid in shape centred around the fibre tip. Maximum diameter of necrosis at 4 days was 12mm using 3W ×333 s.(n=15) Histology demonstrated well demarcated thermal necrosis at 4 days and by 6 months showed a small fibrous granuloma surrounding remnants of charred tissue. In groups of at least 4 animals using 2W250s,mean lesion sizes at 4,10,60 120 and 180 days were 5.5,5.5,3.5,4.5 and 4 mm respectively. 8 of 60 rats developed pneumothorax,due in 5 cases to laser effect at the proximal end of the fibre causing a hole in the chest wall in these small animals The acute effects of ILP on the lung are comparable to that seen in other organs and there is satisfactory long term healing.The low incidence of pneumothorax may be due to a sealing effect on the lung by the laser . Multiple fibres could be used simultaneously. Conclusion: ILP is safe in normal lung parenchyma and may be appropriate for treating small peripheral tumours.
Pregnancy outcome and survivorship in cancer patients.
Authors: Nir Pillar, Shali Mazaki-Tovi, Raanan Berger, Shani Paluch-Shimon, Zvi Symon, Yaacov Richard Lawrence
Journal: Journal of Clinical Oncology (2013)

1503 Background: Advances in cancer detection and treatment have resulted in increased prevalence of female cancer survivors at childbearing age. While the association between cancer treatment and fertility has been thoroughly investigated, data regarding pregnancy outcome of cancer survivor are scarce. The aim of this study is to determine whether cancer survivors and sufferers have increased risk of obstetric complications. Methods: A population-based cohort study using data from the NIS of the Healthcare Cost and Utilization Project, focusing on 2000-2006. The rate of maternal and fetal obstetric complications was determined in pregnant women with and without diagnosis of cancer. Results: A total of 6,732,293 births were included in the analysis, of these 15,191 had maternal cancer diagnosis (0.2%). Pregnant women with cancer diagnosis had increased risk for premature labor, ectopic pregnancy, and need for blood transfusion. Moreover, the rate of maternal (3.6/ 1000 births) and fetal (8.3/1000 births) mortality was higher amongst women with cancer compared to non-cancer bearing women- (0.12/ 1000 births) and (3.9/ 1000 births) respectively. Multivariate logistic regression revealed that both age and cancer diagnosis were significantly and independently associated with pregnancy complications. Conclusions: This is the first large-scale study to determine the prevalence of obstetric complications in cancer patients. Pregnant women with a diagnosis of cancer are at increased risk of major obstetric complications, including maternal and fetal death, although the absolute risk is relatively low. It may therefore be prudent to define such pregnancies as “high-risk” and advocate intense prenatal care for these patients. [Table: see text]
IVADo treatment of type II and type III pleuropulmonary blastoma (PPB): A report from the International PPB Registry.
Authors: Leslie Ann Doros, Kris Ann Pinekenstein Schultz, Anne Harris, Gretchen M Williams, John R. Priest, Nicolas Andre, Carlos Rodriguez-Galindo, Louis P Dehner, D Ashley Hill, Yoav H. Messinger
Journal: Journal of Clinical Oncology (2014)

10060 Background: Pleuropulmonary blastoma (PPB) is a rare malignancy of the lung presenting in young children. The International PPB Registry (IPBBR) has pathologically confirmed more than 400 cases of PPB. Three pathologic subtypes correlate with age and outcome: Type I, a purely cystic lesion often cured by surgery alone; Type II, a combined cystic and solid lesion; and Type III, a purely solid high-grade sarcoma. Previously reported five-year survival rates for Types II and III PPB are 67% and 51%, respectively. Historically, treatment for Types II and III PPB has not been uniform. The IPPBR conducted the first prospective treatment study to evaluate the response of Type II and III PPB to a standardized chemotherapy regimen. Methods: Treatment records were obtained forpatients with Type II and III PPB who enrolled on the IPBBR Treatment and Biology registry. A regimen of 36 weeks of ifosfamide, vincristine, actinomycin and doxorubicin (IVADo) was recommended. Sixty-two patients were treated on the IVADo regimen; 42 completed 3 or more cycles of induction IVADo and were considered fully assessable for analyses. The IVADo group was compared as a group to 200 historical IPPBR confirmed PPB patients who received regimens other than IVADo for both event-free survival (EFS) and overall survival (OS). Results: Of the 42 patients, 25 (60%) were males and 17 (40%) females; median age at diagnosis was 35 months (range 19-83). There were 24 (57%) Type II; 4 (10%) Type II/III, and 14 (33%) Type III. At a median follow-up of 28 months (range 2-71), 10 (24%) relapsed; 6 (14%) died at 12-24 months. Compared to the historical group, the IVADo group had better EFS (Log-rank test, p=0.008) and better OS (p=0.04). At 5 years, IVADo had better EFS: 70.8% (95% CI 55.3-86.3%) vs. 44.7% (95% CI 37.1-52.4%), and better OS 79.2% (64.1-94.2%) vs. 60.1% (52.3-67.9%). Conclusions: To date, the IPPBR treatment study represents the only cohort of patients with Type II and Type III PPB that have been treated uniformly. The standardized use of IVADo showed improvement in EFS and OS compared to the historical group. Importantly, the follow-up of the IVADo cohort is shorter, and there are late events and deaths in the historical group, limiting our conclusion. Clinical trial information: NCT01464606.
Pilot study of paclitaxel and carboplatin (P/C) with concurrent radiation therapy (RT) in high risk salivary gland carcinomas (SGC)
Authors: M. Langston, D. Farray, J. C. Ruzich, B. Emami, G. Petruzzelli, J. I. Clark
Journal: Journal of Clinical Oncology (2006)

15538 Background: Standard therapy for high risk SGC includes surgical resection with adjuvant RT, but a high risk of recurrence exists. The role of chemotherapy in this setting has not been fully defined. Methods: This limited institution pilot study evaluated the use of P/C with concurrent RT as adjuvant treatment of high risk SGC. The primary objective was to assess toxicity of this treatment in anticipation of a larger cooperative group phase II study. Eligible patients (pts.) had a Southwest Oncology Group (SWOG) performance status (PS) of 0–2 who after surgical resection of their SGC had high risk features including positive surgical margins, perineural invasion, multiple lymph node (LN) metastases, or extracapsular extension. Treatment included P = 40 mg/m 2 intravenously followed by C = AUC of 2 concurrently on days 1, 8, 15, 22, 29, 36 of RT. RT consisted of a total dose of 60 Gy in 30 fractions to the primary and regional LN sites of disease. Results: Five pts. were enrolled 4 with adenoid cystic CA and 1 with high grade mucoepidermoid CA. Median age was 59 years (32–69), all with SWOG PS = 0. Four pts. completed the full 6 cycle P/C chemotherapy; all completed RT per protocol. Grade III/IV mucositis, the most common toxicity, occurred in 6 of 30 (20%) P/C cycles, leading to alteration of therapy in 1 pt. There was no reported neuropathy or significant laboratory abnormalities. Median follow up was 17.5 months (mos.); most were disease free at last follow up (13 to 37 mos.); 1 recurred at 14 mos.; this pt. accounts for the only death observed. One year survival was 100%. Conclusions: The regimen of P/C with concurrent RT, as defined, was tolerated well. Grade III/IV mucositis was the main toxicity. Based on the overall tolerability of this regimen, we believe that this postoperative combined modality therapy deserves further study in a larger cooperative group phase II trial to further define its toxicity and efficacy in high risk SGC. We thank Bristol Myers Squibb for support of this study. No significant financial relationships to disclose.
Phase I study of combination vemurafenib, carboplatin, and paclitaxel in patients (pts) with <i>BRAF</i>-mutant advanced cancer.
Authors: Shumei Kato, Filip Janku, Sarina Anne Piha-Paul, Aung Naing, Daniel D. Karp, Apostolia Maria Tsimberidou, Vivek Subbiah, Ralph Zinner, Wen-Jen Hwu, Milind M. Javle, Kristin L. Parkhurst, Nishma M. Ramzanali, Razelle Kurzrock, Funda Meric-Bernstam, Young Kwang Chae, Kevin Kim, Gerald Steven Falchook
Journal: Journal of Clinical Oncology (2015)

105 Background: Although BRAF inhibitors have demonstrated efficacy, resistance develops in most pts. We hypothesized that BRAF inhibitor vemurafenib, in combination with carboplatin and paclitaxel, would be well-tolerated and overcome resistance. Methods: We designed a phase I study (3+3 design) to determine safety of vemurafenib (480-960 mg twice a day) with carboplatin (AUC 5-6 q3 weeks) and paclitaxel (75-175 mg/m2 q3 weeks). Endpoints included maximum tolerated dose (MTD), dose limiting toxicity (DLT), and response (RECIST 1.1). Results: To date, 19 pts have enrolled. Pts received vemurafenib (480-720 mg twice a day), carboplatin (AUC 5-6) q3 wks, and paclitaxel (100-135 mg/m2) q3 wks. Median age was 53 yrs (range 33-75) with median of 4 prior systemic therapies (range 1-7). Eleven pts (58%) had received prior BRAF inhibitors, 3 pts (16%) MEK inhibitors, 8 pts (42%) platinum therapy, and 3 pts (16%) taxane therapy. Pts (13/19 [68.4%] with melanoma and n = 1 pt each of cholangiocarcinoma, histiocytoma, papillary thyroid [PTC], anal, unknown primary, pancreatic cancer) had BRAF V600E (n = 15), V600K (n = 1) or other BRAF mutation (n = 1 each for R6712, del N486-P490, and D459G). MTD has not yet been reached. Two pts had DLTs (G2 creatinine elevated >7 days [n = 1], G3 transaminitis and G4 thrombocytopenia [n = 1]). Five pts had grade ≥ 3 drug-related toxicity with neutropenia (n = 5), thrombocytopenia (n = 5), fatigue (n = 4), anemia (n = 3), and hyponatremia (n = 2). Six out of 19 pts (32%) had objective response (all melanoma pts with BRAFV600E [n = 5] and V600K [n = 1] mutation), including 1 complete and 5 partial responses. Four of the 6 responding pts had progressed on prior vemurafenib. Of 11 pts who had received a prior BRAF inhibitor, 4 (36%) achieved objective response. One PTC pt with V600E mutation had prolonged stable disease of 24 months. Among pts with melanoma, response rate was 46% (6/13 pts), with median PFS of 4.9 months (range 0.2–18.4). Conclusions: Combination vemurafenib, carboplatin, and paclitaxel is tolerated in pts with advanced cancer. Responses were observed in melanoma pts previously resistant to BRAF inhibitors, suggesting that the combination may overcome resistance. MTD has not yet been reached, and dose escalation continues. Clinical trial information: NCT01636622.
Personalized cancer therapy for patients with metastatic medullary thyroid cancer (MTC).
Authors: Krzysztof Misiukiewicz, Lewis Winder, Marshall R. Posner, Eric Michael Genden, David Y. Zhang, Ross L Cagan, Michael J Donovan, Eric Schadt
Journal: Journal of Clinical Oncology (2014)

TPS6101 Background: Standard approaches in cancer research identify new therapies based on observed benefit to average populations, but without emphasis on individual patients whose responses can vary considerably. Further, targeted therapies rarely account for the genomic complexity of patient tumors; the result is poor efficacy and rapid resistance. Ideally, we would identify drugs or drug cocktails that (1) target the details of an individual’s tumor and (2) account for its complexity. Models using the fruit fly Drosophila represent a potential new paradigm in cancer therapy. We have developed fly models that can include up to 10 of a patient’s driver mutations; the result is an inexpensive drug screening platform to identify drug cocktails through empirical screening. As validation flies helped identify vandetinib, now approved for treatment of metastatic MTC. Methods: Tumor mutations identified by deep DNA and RNA sequencing of individual tumors are screened for tumor drivers, which are then incorporated into the “personal” Drosophila model and tested against a library of FDA approved drugs. Fly mortality is used as a surrogate for toxicity and increased survival to adulthood; improvements in tumor mutation-linked eye and/or wing abnormalities serve to quantify efficacy. This allows rapid and parallel screening of up to 800 drugs and subsequent drug combinations. The most efficacious and least toxic combinations are tested in xenograft models and a multidisciplinary tumor board of experts select the best therapeutic option. The objective is to demonstrate that the personalized drosophila model approach is superior to the current standard, cabozantinib, which performed best in MTC with a 27% response rate (RR) against placebo in a phase III trial but with considerable toxicity. Using the 27% RR as a benchmark, we will apply a sequential Bayesian method for 50 MTC patients enrolled to receive personalized treatment to demonstrate that this approach has greater efficacy, or at minimum, substantially similar efficacy with reduced toxicity.
Family environment, parent protection, and quality of life in childhood acute lymphoblastic leukemia (ALL) survivors.
Authors: I-Chan Huang, Tara M. Brinkman, Cara I. Kimberg, Ching-Hon Pui, Melissa M. Hudson, Kevin R. Krull
Journal: Journal of Clinical Oncology (2015)

e21027 Background: Parent distress has a negative effect on quality of life (QOL) in childhood cancer survivors, though the effects of family environment and parenting behavior are less understood. This study examined the associations between family conflict, cohesion, parent protective behavior, parent distress, and QOL of ALL survivors. Methods: Long-term survivors of ALL (N = 213; 51.2% male; mean age = 14.8 years; time since diagnosis = 7.7 years) were recruited from St. Jude Children’s Research Hospital. Parent distress, protective behavior, and family conflict and cohesion were measured using the Brief Symptom Inventory-18, Parent Protection Scale, and Family Environment Scale, respectively. Survivors’ physical, emotional, social, and school QOL was reported by parents using the Pediatric Quality of Life Inventory. Associations between parent distress, protective behavior and family environment with child QOL were examined with the correlation analyses. Path analyses were used to identify the direct effect of family environment on child QOL, and the indirect effect through the parent distress and protective behavior after adjusting covariates (child age, gender, and parent education). Results: Correlation analyses indicate greater parent distress was associated with poorer emotional and school QOL (p < 0.01); parent overprotection was associated with poorer emotional QOL (p < 0.01); more family conflict and less cohesion was associated with poorer physical, emotional, and social QOL (p < 0.01); less cohesion was also associated with poorer school QOL (p < 0.01). Path analyses suggest family conflict and cohesion were related to all QOL domains. However, more conflict was associated with poorer emotional and social QOL through the pathway of parent distress and overprotection (p < 0.01); less cohesion was associated with poorer emotional, social, and school functioning through the influence of parent distress and overprotection (p < 0.01). Conclusions: Greater family conflict and less cohesion are related to parent distress and overprotection, which leads to poorer QOL of long-term ALL survivors. Interventions targeted at the family environment may improve survivors’ QOL.
Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis (Journal of Clinical Investigation (2014) 124, 4 (1868) DOI: 10.1172/JCI75669)
Authors: Eric D. Berglund, Chen Liu, Jong Woo Sohn, Tiemin Liu, Mi Hwa Kim, Charlotte E. Lee, Claudia R. Vianna, Kevin W. Williams, Yong Xu, Joel K. Elmquist
Journal: Journal of Clinical Investigation (2014)
Patterns of care and outcome for patients with recurrent glioblastoma (GB).
Authors: Laure De Cock, Quentin Sala, Maryline Barrie, Celine Boucard, Alexia Terciolo, Thomas Graillon, Philippe Metellus, Didier Autran, Emeline Tabouret, Laetitia Padovani, Dominique Figarella-Branger, Henry Dufour, Olivier L. Chinot
Journal: Journal of Clinical Oncology (2014)

e13007 Background: Access to salvage treatment for patients with recurrent GB is poorly documented in daily practice. Our objective was to assess patterns of care and outcome in patients with recurrent GB. Methods: A retrospective analysis of consecutive patients with histologically proven GB treated in 2008 and 2011 at Timone University Hospital was performed. Clinical, therapeutic and outcome data were collected. Results: 207 patients were identified (2008: n=99; 2011: n=108). Patient’s characteristics, pattern of care and outcome were similar between 2008 and 2011 and, therefore analyzed together. Overall survival from initial diagnosis (OSI) was 15.0 months (95% CI 12.9-17.1). Recurrence was diagnosed in 158 pts (76.3%). Overall survival from recurrence (OSR) was 6.6 months (95% CI 5.6-7.5). 117/158 pts (74%) of them received salvage treatment; 41 (26%) received no trt. 53, 48, and 16 pts received 1, 2 and > 2 lines at recurrence respectively. 2line treatment consist of chemotherapy (CT), n=23 (19.7%), bevacizumab (BEV) +/- CT, n=63 (53.8%), surgery +/- carmustine wafer (CW), n=16 (10.1%), reirradiation (RRT) (1) and inclusion in clinical trials, n=16 (9.5%). OSR in patient treated with CT+/-BEV was 8.0 months (95% CI 6.9-9.1) and OSI was 18.9 months (95% CI 16.3-21.5). OSR in patients with local treatment (surgery +/-CW, RRT) was 10.8 months (95% CI 7.7-13.8); OSI was 29.7 months (CI 95% 10.5-39). In pts who received no salvage trt, OSR and OSI were 1.8 (95% CI 1.4-2.1) and 7.5 (95% CI 6.4-8.6) months respectively. In patients aged over 70 years (n=76), recurrence was determined in 50 of whom 30 (60%) received a salvage treatment. OSR was 5.2 months (95% CI 3.9-6.6) and OSI was 8.9 months (95% CI 7.5-10.4). In pts aged ≤ 70years (n=131), recurrence was determined in 108 of whom 87 (81%) received a treatment at progression. OSR was 7.1 months (95% CI 5.9-8.4) and OSI was 18.1 months (95% CI 15.2-21.0). Conclusions: In a center assuming mainly primary care of patients, 75% of the pts identified with recurrent GB received salvage treatment. Differences in outcome associated to systemic treatment, second surgery, and no treatment could be related to pts/tumor heterogeneity and treatment. Access to and results of salvage treatment in elderly are limited.
Association of clinical complete response (cCR) after preoperative chemoradiation and pathological complete response (pathCR) in patients with gastroesophageal cancer (GEC) and indispensability of trimodality therapy (TMT).
Authors: Naga K Sucharita Cheedella, Akihiro Suzuki, Arlene M Correa, Wayne Lewis Hofstetter, Reza J. Mehran, David C. Rice, Dipen M Maru, Ara A. Vaporciyan, Takashi Taketa, Mariela A. Blum, James Welsh, Steven H. Lin, Jeffrey H Lee, Manoop S. Bhutani, Brian Weston, Garrett L Walsh, Stephen Swisher, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2012)

4086 Background: TMT strategy has the highest level-1 evidence for treating localized GEC. High rates of cCR (defined as post-chemoradiation negative endoscopic biopsy and physiologic uptake on PET) are common and have questioned the benefit from surgery in patients with cCR after chemoradiation. We hypothesized that cCR would be associated with a high rate of pathCR than &lt; cCR. Methods: The data were analyzed retrospectively in 563 patients who had esophagectomy for GEC in between 2002 and 2010 at UTMDACC. Among them, 284 had TMT and post-chemoradiation endoscopic biopsies and PET (before surgery). Multiple statistical methods were used. Results: Of these 284 TMT patients, 218 (77%) patients achieved a cCR. However, only 67 (31%) of 218 had a pathCR. The sensitivity of cCR for pathCR was 97.1 % (67/69) but the specificity was low, 29.8 % (64/215). Intriguingly, 66 patients who had &lt; cCR, only 2 patients (3%) had a pathCR. The difference in the rate of pathCR between the cCR and &lt; cCR groups was significant (P &lt; 0.001). Conclusions: Our data show that cCR is frequent after chemoradiation but the pathCR rate is not high and it is associated with specificity that is too low for clinical implementation. Therefore, all TMT-eligible patients, irrespective of the achievement of cCR or &lt; cCR must be encouraged to undergo surgery. Therapies that overcome chemoradiation resistance and could increase the pathCR rate are needed for esophageal preservation in select GEC patients. Supported by UTMDACC and generous donors. [Table: see text]
A phase II multicenter trial comparing two schedules of lapatinib (LAP) as first or second line monotherapy in subjects with advanced or metastatic non-small cell lung cancer (NSCLC) with either bronchioloalveolar carcinoma (BAC) or no smoking history
Authors: M. Smylie, G. R. Blumenschein, A. Dowlati, J. Garst, F. A. Shepherd, J. R. Rigas, H. Hassani, M. S. Berger, T. Zaks, H. J. Ross
Journal: Journal of Clinical Oncology (2007)

7611 Background: LAP (GW572016) is an oral reversible, dual tyrosine kinase inhibitor of EGFR (ERBB1) and HER2/neu (ERBB2). This study was designed to test the activity of 2 dose schedules of LAP in chemotherapy naïve pts with NSCLC; it was amended to target patients with either BAC or no smoking history in the first or second line and to evaluate the relationship of mutations in target genes to responses. Methods: LAP was given orally 1,500 mg once (QD) or 500 mg twice daily (BID) until progression or intolerance. Safety and efficacy (RECIST) were assessed every 4 &amp; 8 weeks. The primary endpoint was response. The target (BAC/no smoking) and non- target populations were assessed for efficacy, and tumor tissue was analyzed for ERBB1 and ERBB2 mutations and/or amplifications. Results: The study was stopped for futility after 131 pts were randomized (65 QD, 66 BID). Median age 66 (range 32–86); female 56%; BAC 20%, No BAC 71%; previously untreated 98.5%; current/former smokers 70%, never smoker 30%. There were no complete responses. Of 56 pts in the target population, 1 (2%) achieved partial response (PR), 11 (20%) had stable disease (SD) of ≥24 wks; in the non-target population, 1 pt had a PR (1.3%) and 12 (16%) had SD of ≥24 wks. 3 pts had ERBB1 mutations (G719S, S768I, KRAS G12S; L858R and T790M; L858R) but none of them responded. There were no ERBB2 mutations. Three of 77 pts evaluated had ERBB1 gene copy increase (none of whom responded) and 2 had ERBB2 gene copy increase (one had a 51% decrease in tumor size). The most common adverse events were grade 1/2 diarrhea, nausea, rash, vomiting and fatigue, and were similar in both groups. Conclusions: LAP was well-tolerated, with no notable difference in toxicity between the QD and BID groups. Very few responses were seen, stable disease was sometimes prolonged. The prevalence of mutations was low even in the target population. Given the preclinical synergy between LAP and other agents, further studies will be necessary to determine whether LAP is active in combination with other agents for the treatment of NSCLC. [Table: see text]