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Braunstein L.Z.,Harvard University | Chen M.-H.,University of Connecticut | Dosoretz D.E.,21st Century Oncology | Salenius S.A.,21st Century Oncology | And 3 more authors.
Clinical Genitourinary Cancer | Year: 2015

Background The purpose of the study was to determine whether the extent of prostate radiotherapy (ie, whole-pelvic radiotherapy [WPRT] vs. prostate and seminal vesicle radiotherapy [PSVRT]) is associated with all-cause mortality (ACM) in men treated with or without androgen deprivation therapy (ADT). Patients and Methods A multiple-institution cohort of 3709 prostate cancer patients was prospectively assembled from 1991 to 2006. The median age was 72 years and all patients had T1c-T3N0M0 adenocarcinoma of the prostate. Patients were treated with WPRT or PSVRT followed by a brachytherapy boost, with or without neoadjuvant ADT (median duration, 4.2 months). Seventy percent of patients had unfavorable-risk disease (Gleason score ≥7; prostate-specific antigen ≥10 ng/mL; or stage ≥T2b). Cox regression was applied to determine whether the radiation treatment volume affected the risk of ACM. The interaction between radiation volume and ADT use was assessed. Results After a median follow-up of 3.3 years, 561 deaths were observed. A decreased risk of ACM was noted with the use of WPRT versus PSVRT (adjusted hazard ratio [AHR], 0.58; 95% confidence interval [CI], 0.38-0.89; P =.01), or with ADT use (AHR, 0.71; 95% CI, 0.58-0.90; P =.004). However, a combination of WPRT and ADT did not further improve ACM compared with either WPRT alone or PSVRT with ADT. Moreover, there was a significant interaction between the radiotherapeutic treatment volume and ADT (AHR, 1.61; 95% CI, 1.004-2.58; P =.048). Conclusion Treatment with WPRT or short-course ADT is associated with a decreased risk of ACM, although a combination of the two does not yield greater benefit. This observation suggests a shared mechanism for this risk reduction, which we hypothesize to be via the treatment of micrometastatic disease within the pelvic lymph nodes. © 2015 Elsevier Inc. All rights reserved.


PubMed | Health Cancer Center, Brigham and Women's Hospital, 21st Century Oncology, Harvard University and University of Connecticut
Type: Comparative Study | Journal: Clinical genitourinary cancer | Year: 2015

The purpose of the study was to determine whether the extent of prostate radiotherapy (ie, whole-pelvic radiotherapy [WPRT] vs. prostate and seminal vesicle radiotherapy [PSVRT]) is associated with all-cause mortality (ACM) in men treated with or without androgen deprivation therapy (ADT).A multiple-institution cohort of 3709 prostate cancer patients was prospectively assembled from 1991 to 2006. The median age was 72 years and all patients had T1c-T3N0M0 adenocarcinoma of the prostate. Patients were treated with WPRT or PSVRT followed by a brachytherapy boost, with or without neoadjuvant ADT (median duration, 4.2 months). Seventy percent of patients had unfavorable-risk disease (Gleason score 7; prostate-specific antigen 10 ng/mL; or stage T2b). Cox regression was applied to determine whether the radiation treatment volume affected the risk of ACM. The interaction between radiation volume and ADT use was assessed.After a median follow-up of 3.3 years, 561 deaths were observed. A decreased risk of ACM was noted with the use of WPRT versus PSVRT (adjusted hazard ratio [AHR], 0.58; 95% confidence interval [CI], 0.38-0.89; P = .01), or with ADT use (AHR, 0.71; 95% CI, 0.58-0.90; P = .004). However, a combination of WPRT and ADT did not further improve ACM compared with either WPRT alone or PSVRT with ADT. Moreover, there was a significant interaction between the radiotherapeutic treatment volume and ADT (AHR, 1.61; 95% CI, 1.004-2.58; P = .048).Treatment with WPRT or short-course ADT is associated with a decreased risk of ACM, although a combination of the two does not yield greater benefit. This observation suggests a shared mechanism for this risk reduction, which we hypothesize to be via the treatment of micrometastatic disease within the pelvic lymph nodes.


PubMed | Orlando Health, Health Cancer Center and Halifax Regional Oncology Center
Type: Journal Article | Journal: Case reports in oncology | Year: 2014

Cutaneous drug reactions make up the largest proportion of adverse events in the medical field. Causality, in particular, is difficult to determine, and therefore, preventing recurrent reactions can be challenging. Bendamustine was initially thought to be a well-tolerated chemotherapy agent with few side effects aside from bone marrow suppression. However, the incidence of cutaneous reactions reported is rising. We describe three such reactions in relation to bendamustine administration in hopes of adding to the awareness of such side effects.


Pogue-Geile K.L.,National Surgical Adjuvant Breast and Bowel Project | Song N.,National Surgical Adjuvant Breast and Bowel Project | Jeong J.-H.,Data Management | Jeong J.-H.,University of Pittsburgh | And 22 more authors.
Journal of Clinical Oncology | Year: 2015

Purpose: Considerable molecular heterogeneity exists among human epidermal growth factor receptor 2 (HER2) -positive breast cancer regarding gene expression and mutation profiling. Evidence from preclinical, clinical neoadjuvant, and metastatic clinical trials suggested that PIK3CA mutational status and PAM50 intrinsic subtype of a tumor were markers of response to anti-HER2 therapies. We evaluated the predictive value of these two biomarkers in the adjuvant setting using archived tumor blocks from National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31. Patients and Methods: Expression data for 49 genes using the nCounter platform were used to generate PAM50 intrinsic subtypes for 1,578 archived tumor blocks from patients in the B-31 trial. Six PIK3CA hotspot mutations were examined by mass spectrometry of the primer extension products in a randomly selected subset (n = 671). We examined the heterogeneity of trastuzumab treatment effect across different subsets defined by each marker using Cox regression and disease-free survival as the end point. Results: Seven hundred forty-one (47.0%) of 1,578 tumors were classified as HER2-enriched (HER2E) subtype, and 166 (24.7%) of 671 tumors had PIK3CA mutations. Hazard ratios (HRs) for trastuzumab in HER2E and other subtypes were 0.44 (95% CI, 0.34 to 0.58; P < .001) and 0.47 (95% CI, 0.35 to 0.62; P < .001), respectively (interaction P = .67). HRs for trastuzumab in PIK3CA wild-type and mutated tumors were 0.51 (95% CI, 0.37 to 0.71; P < .001) and 0.44 (95% CI, 0.24 to 0.82; P = .009), respectively (interaction P = .64). Conclusion: Unlike results seen in the metastatic and neoadjuvant clinical trials, PIK3CA and PAM50 intrinsic subtypes were not predictive biomarkers for adjuvant trastuzumab in NSABP B-31. These data suggest that results from the metastatic and neoadjuvant setting may not be always applicable to the adjuvant setting. © 2015 by American Society of Clinical Oncology.


Starodub A.N.,Indiana University | Ocean A.J.,New York Presbyterian Hospital | Shah M.A.,New York Presbyterian Hospital | Guarino M.J.,Christiana Care Health System Graham Cancer Center | And 9 more authors.
Clinical Cancer Research | Year: 2015

Purpose: Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) targeting Trop-2, a surface glycoprotein expressed on many epithelial tumors, for delivery of SN-38, the active metabolite of irinotecan. This phase I trial evaluated this ADC as a potential therapeutic for pretreated patients with a variety of metastatic solid cancers. Experimental Design: Sacituzumab govitecan was administered on days 1 and 8 of 21-day cycles, with cycles repeated until dose-limiting toxicity or progression. Dose escalation followed a standard 3 + 3 scheme with 4 planned dose levels and dose delay or reduction allowed. Results: Twenty-five patients (52-60 years old, 3 median prior chemotherapy regimens) were treated at dose levels of 8 (n = 7), 10 (n = 6), 12 (n = 9), and 18 (n = 3) mg/kg. Neutropenia was dose limiting, with 12 mg/kg the maximum tolerated dose for cycle 1, but too toxic with repeated cycles. Lower doses were acceptable for extended treatment with no treatment-related grade 4 toxicities and grade 3 toxicities limited to fatigue (n = 3), neutropenia (n = 2), diarrhea (n = 1), and leukopenia (n = 1). Using CT-based RECIST 1.1, two patients achieved partial responses (triple-negative breast cancer, colon cancer) and 16 others had stable disease as best response. Twelve patients maintained disease control with continued treatment for 16 to 36 weeks; 6 survived 15 to 20+ months. No preselection of patients based on tumor Trop-2 expression was done. Conclusions: Sacituzumab govitecan had acceptable toxicity and encouraging therapeutic activity in patients with difficult-to-treat cancers. The 8 and 10 mg/kg doses were selected for phase II studies. © 2015 American Association for Cancer Research.


George T.J.,Florida College | Roh M.S.,Health Cancer Center
ONCOLOGY (United States) | Year: 2016

By adjusting the sequencing of currently available treatments, improved compliance with therapy is ensured, and novel scientific and clinically relevant hypotheses can be further explored. © 2016, UBM Medica Healthcare Publications. All rights reserved.


Szaniszlo P.,301 University Blvd | Szaniszlo P.,Health Cancer Center | Fennewald S.M.,301 University Blvd | Fennewald S.M.,Health Cancer Center | And 7 more authors.
Head and Neck | Year: 2014

Background The overall mortality rate in cases of head and neck squamous cell carcinoma (HNSCC) has not improved over the past 30 years, mostly because of the high treatment failure rate among patients with regionally metastatic disease. To better understand the pathobiologic processes leading to lymphatic metastasis development, there is an urgent need for relevant animal models. Methods HNSCC cell lines were implanted into the tongues of athymic nude mice. Histology, immunohistochemistry, and ex vivo 2-photon microscopy were used to evaluate tumor progress and spread. Results Orthotopic xenografts of different HNSCC cell lines produced distinct patterns of survival, tumor histology, disease progression rate, and lymph node metastasis development. Remarkably, all injected cell types reached the lymph nodes within 24 hours after injection, but not all developed metastasis. Conclusion This orthotopic xenograft model closely mimics several characteristics of human cancer and could be extremely valuable for translational studies focusing on lymphatic metastasis development and pathobiology. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1638-1647, 2014 © 2014 Wiley Periodicals, Inc.


Manon R.,Health Cancer Center | Zeidan O.,Health Cancer Center | Pukala J.,Health Cancer Center | Hsi W.,Proton Therapy | Staton R.,Health Cancer Center
Current Cancer Therapy Reviews | Year: 2014

Radiation therapy has been a major modality employed in the treatment of head and neck (H&N) cancer for decades. In that time, radiation technology has evolved considerably. Thirty years ago radiation therapy for H&N cancer consisted of two-dimensional techniques using plain field radiographs, bony anatomy, and hand drawn blocks [1]. Beam set ups were generally quite simple and plans generally consisted of opposed lateral fields matched to an anteroposterior supraclavicular field. Nearly a decade later, several technologic developments combined to catapult radiation therapy into a new era. Three-dimensional imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) were integrated with radiation planning technologies creating three-dimensional conformal radiation therapy (3DCRT). The CT simulator rapidly came to replace the x-ray simulator. With CT simulation, the radiation oncologist could now take into account axial anatomy; thereby more accurately identify tumor volumes and institute more complex beam arrangements in treatment planning [2].  During the decade that followed, the cerrobend block was replaced by the multileaf collimator and advances in computer optimization algorithms gave birth to intensity modulated radiation therapy (IMRT). This technological improvement allowed us to modulate the number of radiation fields and the intensity of radiation within each field. Instead of the physician choosing the beam angle, block, and weighting, computer optimization techniques would create a distribution of beamlets based on dose parameters to contoured structures (a process referred as inverse planning) [3, 4]. IMRT changed the practice of radiation oncology by providing the user unprecedented ability to sculpt the radiation dose. Since the advent of IMRT there have been several “technological advances.” Image guided radiation therapy (IGRT), adaptive radiation therapy (ART), and now proton therapy (PRT) represent new technologies that are either actively used or being incorporated into the treatment of H&N cancer. The H&N region is an ideal site to examine a new radiation treatment paradigm. The tissues in the H&N are exquisitely sensitive to the acute and late effects of radiation treatment. Even in the present day, toxicities such as mucositis, dermatitis, soft tissue fibrosis, and xerostomia commonly arise from irradiation of the H&N [5-7]. Head and neck cancer patients historically face long-term difficulties with eating, speaking, tasting, dry mouth, decreased range of motion, and wound healing [8, 9]. Radiation treatment of H&N cancer bears a high toxicity burden. Therefore, technological advances that improve conformity and precision of radiation delivery have been employed to decrease side effects in this patient population. The questions that bear asking are “what have we gained from these advancements in the last 30 years and what are the next steps?” © 2014 Bentham Science Publishers.


The biologic rationale for the initial evaluation of preoperative chemotherapy or neoadjuvant chemotherapy in patients with early-stage breast cancer was based on experimental and clinical observations regarding primary tumor cell growth and dissemination. © 2015, UBM Medica Healthcare Publications. All rights reserved.


PubMed | Health Cancer Center
Type: Journal Article | Journal: Head & neck | Year: 2014

The overall mortality rate in cases of head and neck squamous cell carcinoma (HNSCC) has not improved over the past 30 years, mostly because of the high treatment failure rate among patients with regionally metastatic disease. To better understand the pathobiologic processes leading to lymphatic metastasis development, there is an urgent need for relevant animal models.HNSCC cell lines were implanted into the tongues of athymic nude mice. Histology, immunohistochemistry, and ex vivo 2-photon microscopy were used to evaluate tumor progress and spread.Orthotopic xenografts of different HNSCC cell lines produced distinct patterns of survival, tumor histology, disease progression rate, and lymph node metastasis development. Remarkably, all injected cell types reached the lymph nodes within 24 hours after injection, but not all developed metastasis.This orthotopic xenograft model closely mimics several characteristics of human cancer and could be extremely valuable for translational studies focusing on lymphatic metastasis development and pathobiology.

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