Implications of metastatic stage at presentation in docetaxel naïve metastatic castrate resistant prostate cancer.

BACKGROUND: We performed a secondary analysis of ACIS study to determine if synchronous versus metachronous metastatic presentation has any association with survival and treatment response to dual androgen receptor axis-targeted therapy (ARAT) in docetaxel naïve metastatic castrate resistant prostate cancer (mCRPC). METHODOLOGY: In this phase III randomized controlled trial, docetaxel naïve mCRPC patients were randomized to either apalutamide or placebo combined with abiraterone and prednisone. Multivariable Cox regression models were applied to determine the adjusted association of M-stage with radiographic progression-free survival (rPFS) and overall survival (OS). To determine the heterogeneity of treatment effect based on metastatic stage (M-stage) at presentation, Cox regression was applied with interaction terms between M-stage and treatment. RESULTS: Among 972 patients, 432 had M0, 334 had M1, while M-stage at presentation was unknown in 206. There was no association of M-stage at presentation with rPFS in patients with prior local therapy (LT) (hazard ratio for M1-stage: 1.22 [95% confidence interval: 0.82-1.82]; unknown: 1.03 [0.77-1.38]) or without prior LT (M1-stage: 0.87 [0.64-1.19]; unknown: 1.15 [0.77-1.72]) with no significant heterogeneity. Similarly, there was no association of M-stage with OS in patients with prior LT (M1-stage: 1.04 [0.81-1.33]; unknown: 0.98 [0.79-1.21]) or without prior LT (M1-stage: 0.95 [0.70-1.29]; unknown: 1.17 [0.80-1.71]) with no significant heterogeneity. Based on M-stage at presentation, we did not find any significant heterogeneity in treatment effect on rPFS (interaction p = 0.13), and OS (interaction p = 0.87). CONCLUSION: M-stage at presentation had no association with survival in chemotherapy-naïve mCRPC. We did not find any statistically significant heterogeneity in efficacy of dual ARAT based on synchronous versus metachronous presentation.

Poly(adenosine diphosphate-ribose) polymerase inhibitor combinations in first-line metastatic castrate-resistant prostate cancer setting: a systematic review and meta-analysis.

OBJECTIVES: To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving a combination of first-line poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) plus androgen receptor axis-targeted agents (ARAT) vs placebo/ARAT. MATERIALS AND METHODS: We conducted a systematic review/meta-analysis of all published Phase III randomised controlled trials using EMBASE, MEDLINE, and Cochrane (inception until 6 June 2023). Published full-text manuscripts and conference abstracts were inclusion eligible. Study selection/data extraction were independently performed by two authors. The Cochrane Risk-of-Bias 2 Tool was used, and certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Pooled hazard ratios (HRs) and relative risks, with corresponding confidence intervals (CIs), were generated using random-effects models. RESULTS: Three trials were identified: PROpel, MAGNITUDE, and TALAPRO-2. Compared to placebo/ARAT, the PARPi/ARAT combination was associated with a 35% rPFS improvement in the overall cohort (HR 0.65, 95% CI 0.56-0.76), with 68%, 45%, and 26% improvements in the BReast CAncer gene 1/gene 2 (BRCA1/2)-mutated (BRCA1/2m; P < 0.001), homologous recombination repair-mutated (HRRm; P < 0.001), and non-HRRm cohorts (P = 0.003), respectively. OS data maturity ranged from 31% to 48%, with overall cohort OS data unavailable from MAGNITUDE. The PROpel/TALAPRO-2 pooled analysis demonstrated a 16% OS improvement in the overall cohort (HR 0.84, 95 CI 0.72-0.98; P = 0.02). OS in the HRRm (HR 0.76, 95% CI 0.61-0.95) and the BRCA1/2m cohorts (HR 0.53, 95% CI 0.18-1.56) were improved, with a higher effect magnitude compared to the overall cohort. This combination was associated with a 45% relative risk increase in Grade ≥3 TEAEs, including 6.22-fold for Grade ≥3 anaemia (31.9% vs 4.9%). CONCLUSIONS: The addition of PARPi to ARAT in the first-line mCRPC setting is associated with rPFS benefits across subgroups, with the greatest magnitude of benefit in BRCA1/2m patients. OS benefits remain inconsistent irrespective of HRRm status, with significant increases in Grade ≥3 TEAEs, particularly anaemia. Currently, we suggest this combined approach be selectively offered to HRRm patients, preferentially BRCA1/2m.

Association of PSA kinetics after testosterone recovery with subsequent recurrence: secondary analysis of a phase III randomized controlled trial.

PURPOSE: After cessation of androgen deprivation therapy (ADT), testosterone gradually recovers to supracastrate levels (> 50 ng/dL). After this, rises in prostate-specific antigen (PSA) are often seen. However, it remains unknown whether early PSA kinetics after testosterone recovery are associated with subsequent biochemical recurrence (BCR). METHODS: We performed a secondary analysis of a phase III randomized controlled trial in which newly diagnosed localized prostate cancer patients were randomly allocated to ADT for 6 months starting 4 months prior to or simultaneously with prostate RT. We calculated the PSA doubling time (PSADT) based on PSA values up to 18 months after supracastrate testosterone recovery. Competing risk regression was used to evaluate the association of PSADT with relative incidence of BCR, considering deaths as competing events. RESULTS: Overall, 313 patients were eligible. Median PSADT was 8 months. Cumulative incidence of BCR at 10 years from supracastrate testosterone recovery was 19% and 11% in patients with PSADT < 8 months and ≥ 8 months (p = 0.03). Compared to patients with PSADT of < 4 months, patients with higher PSADT (sHR for PSADT 4 to < 8 months: 0.36 [95% CI 0.16-0.82]; 8 to < 12 months: 0.26 [0.08-0.91]; ≥ 12 months: 0.20 [0.07-0.56]) had lower risk of relative incidence of BCR. CONCLUSIONS: Early PSA kinetics, within 18 months of recovery of testosterone to a supracastrate level, can predict for subsequent BCR. Taking account of early changes in PSA after testosterone recovery may allow for recognition of potential failures earlier in the disease course and thereby permit superior personalization of treatment.

Impact of sequencing of androgen receptor-signaling inhibition and radiotherapy in prostate cancer: importance of homologous recombination disruption.

PURPOSE: The synergy of combining androgen receptor-signaling inhibition (ARSI) to radiotherapy (RT) in prostate cancer has been largely attributed to non-homologous end joining (NHEJ) inhibition. However, this mechanism is unlikely to explain recently observed trial results that demonstrated the sequencing of ARSI and RT significantly impacts clinical outcomes, with adjuvant ARSI following RT yielding superior outcomes to neoadjuvant/concurrent therapy. We hypothesized this is driven by differential effects on AR-signaling and alternative DNA repair pathway engagement based on ARSI/RT sequencing. METHODS: We explored the effects of ARSI sequencing with RT (neoadjuvant vs concurrent vs adjuvant) in multiple prostate cancer cell lines using androgen-deprived media and validation with the anti-androgen enzalutamide. The effects of ARSI sequencing were measured with clonogenic assays, AR-target gene transcription and translation quantification, cell cycle analysis, DNA damage and repair assays, and xenograft animal validation studies. RESULTS: Adjuvant ARSI after RT was significantly more effective at killing colony forming cells and decreasing the transcription and translation of downstream AR-target genes across all prostate cancer models evaluated. These results were reproduced in xenograft studies. The differential effects of ARSI sequencing were not fully explained by NHEJ inhibition alone, but by the additional disruption of homologous recombination specifically with adjuvant sequencing of ARSI. CONCLUSION: We demonstrate that altered sequencing of ARSI and RT mediates differential anti-AR-signaling and anti-cancer effects, with the greatest benefit from adjuvant ARSI following RT. These results, combined with our prior clinical findings, support the superiority of an adjuvant-based sequencing approach when using ARSI with RT.

Lipid-induced monokine cyclophilin-A promotes adipose tissue dysfunction implementing insulin resistance and type 2 diabetes in zebrafish and mice models of obesity.

Several studies have implicated obesity-induced macrophage-adipocyte cross-talk in adipose tissue dysfunction and insulin resistance. However, the molecular cues involved in the cross-talk of macrophage and adipocyte causing insulin resistance are currently unknown. Here, we found that a lipid-induced monokine cyclophilin-A (CyPA) significantly attenuates adipocyte functions and insulin sensitivity. Targeted inhibition of CyPA in diet-induced obese zebrafish notably reduced adipose tissue inflammation and restored adipocyte function resulting in improvement of insulin sensitivity. Silencing of macrophage CyPA or pharmacological inhibition of CyPA by TMN355 effectively restored adipocytes' functions and insulin sensitivity. Interestingly, CyPA incubation markedly increased adipocyte inflammation along with an impairment of adipogenesis, however, mutation of its cognate receptor CD147 at P309A and G310A significantly waived CyPA's effect on adipocyte inflammation and its differentiation. Mechanistically, CyPA-CD147 interaction activates NF-κB signaling which promotes adipocyte inflammation by upregulating various pro-inflammatory cytokines gene expression and attenuates adipocyte differentiation by inhibiting PPARγ and C/EBPß expression via LZTS2-mediated downregulation of ß-catenin. Moreover, inhibition of CyPA or its receptor CD147 notably restored palmitate or CyPA-induced adipose tissue dysfunctions and insulin sensitivity. All these results indicate that obesity-induced macrophage-adipocyte cross-talk involving CyPA-CD147 could be a novel target for the management of insulin resistance and type 2 diabetes.

Directed Self-Assembly Driven Mesoscale Lithography Using Laser-Induced and Manipulated Microbubbles: Complex Architectures and Diverse Applications.

A microbubble nucleated due to the absorption of a tightly focused laser at the interface of a liquid-solid substrate enables directed and irreversible self-assembly of mesoscopic particles dispersed in the liquid at the bubble base. This phenomenon has facilitated a new microlithography technique which has grown rapidly over the past decade and can now reliably pattern a vast range of soft materials and colloids, ranging from polymers to metals to proteins. In this review, we discuss the science behind this technology and the present state-of-the-art. Thus, we describe the physics of the self-assembly driven by the bubble, the techniques for generating complex mesoarchitectures, both discrete and continuous, and their properties, and the various applications demonstrated in plastic electronics, site-specific catalysis, and biosensing. Finally, we describe a roadmap for the technique to achieve its potential of successfully patterning "everything" mesoscopic and the challenges that lie therein.

An Anthracene-Based Metal-Organic Framework for Selective Photo-Reduction of Carbon Dioxide to Formic Acid Coupled with Water Oxidation.

A Zr-based metal-organic framework has been synthesized and employed as a catalyst for photochemical carbon dioxide reduction coupled with water oxidation. The catalyst shows significant carbon dioxide reduction property with concomitant water oxidation. The catalyst has broad visible light as well as UV light absorption property, which is further confirmed from electronic absorption spectroscopy. Formic acid was the only reduced product from carbon dioxide with a turn-over frequency (TOF) of 0.69 h-1 in addition to oxygen, which was produced with a TOF of 0.54 h-1 . No external photosensitizer is used and the ligand itself acts as the light harvester. The efficient and selective photochemical carbon dioxide reduction to formic acid with concomitant water oxidation using Zr-based MOF as catalyst is thus demonstrated here.

Adjuvant Treatment of Early Ovarian Clear Cell Carcinoma: A Population-Based Study of Whole Abdominal Versus Pelvic Nodal Radiotherapy.

BACKGROUND: Adjuvant treatment in early ovarian clear cell carcinoma (OCCC) is not yet standardized. The objective of this population-based study was to compare the outcome of patients with early OCCC treated with adjuvant chemotherapy versus chemoradiotherapy (chemoRT) and evaluate the association of adjuvant radiotherapy regimens (whole abdominal radiotherapy [WART] versus pelvic nodal radiotherapy [PRT]) with outcome. PATIENTS AND METHODS: Chart review was conducted to identify patients with stage I and II OCCC with complete information on staging. Patients with stage IA, IB, or IC OCCC purely resulting from capsular rupture were excluded because the provincial protocol does not recommend adjuvant treatment. RESULTS: Overall, 403 patients were identified and 343 received adjuvant treatment, of whom 255 had stage IC or II OCCC and 153 were eligible for final analysis. On Cox multivariable regression, receipt of chemoRT (n=90) was associated with an improvement in failure-free survival (FFS) (hazard ratio [HR], 0.57; 95% CI, 0.34-0.94) compared with chemotherapy alone (n=63). Use of chemoRT also resulted in 54% reduction in the cumulative incidence of cancer-specific mortality (subdistribution HR, 0.46; 95% CI, 0.24-0.89). However, there was no significant difference in the HR for overall survival (OS) between the chemoRT (HR, 0.70; 95% CI, 0.43-1.13) and chemotherapy group. Relative to chemotherapy + WART (chemo-WART), chemotherapy + PRT (chemo-PRT) was not associated with any significant difference in HR for FFS (HR, 1.34; 95% CI, 0.40-4.44) or OS (HR, 1.13; 95% CI, 0.37-3.46). CONCLUSIONS: Adjuvant chemoRT was associated with a lower risk of failure compared with chemotherapy alone. However, there was no difference in OS between the adjuvant chemotherapy and chemoRT regimens. Additionally, no significant difference in terms of FFS or OS was found between the chemo-WART and chemo-PRT groups.

Electrocatalytic Reduction of CO2 to Acetic Acid by a Molecular Manganese Corrole Complex.

The controlled electrochemical reduction of carbon dioxide to value added chemicals is an important strategy in terms of renewable energy technologies. Therefore, the development of efficient and stable catalysts in an aqueous environment is of great importance. In this context, we focused on synthesizing and studying a molecular MnIII -corrole complex, which is modified on the three meso-positions with polyethylene glycol moieties for direct and selective production of acetic acid from CO2 . Electrochemical reduction of MnIII leads to an electroactive MnII species, which binds CO2 and stabilizes the reduced intermediates. This catalyst allows to electrochemically reduce CO2 to acetic acid in a moderate acidic aqueous medium (pH 6) with a selectivity of 63 % and a turn over frequency (TOF) of 8.25 h-1 , when immobilized on a carbon paper (CP) electrode. In terms of high selectivity towards acetate, we propose the formation and reduction of an oxalate type intermediate, stabilized at the MnIII -corrole center.

Hypofractionated Radiotherapy for Localized Prostate Cancer: When and for Whom?

PURPOSE OF REVIEW: To summarize recent evidence concerning the use of moderately hypofractionated external beam radiotherapy, defined as 2.4-3.4 Gy per fraction, and ultrahypofractionated external beam radiotherapy (also known as stereotactic body radiotherapy [SBRT]), defined as at least 5 Gy per fraction, in men with localized prostate cancer. RECENT FINDINGS: Taken together, a number of recently completed randomized trials show that moderately hypofractionated radiotherapy confers similar biochemical control compared to conventionally fractionated radiotherapy without increasing late toxicity. These effects appear to extend across all baseline clinical risk groups. Several single-arm phase II studies, as well as a recently published large-scale randomized trial comparing SBRT with conventional fractionation, show very promising biochemical control and favorable acute and late treatment-related morbidity with the use of SBRT in predominantly low- and intermediate-risk prostate cancer. As it is associated with similar prostate cancer control and toxicity while improving patient convenience and reducing cost, moderate hypofractionation is a preferred alternative to conventional fractionation in a majority of men with localized prostate cancer choosing radiotherapy as their primary treatment modality. To date, studies conducted largely in low- and intermediate-risk prostate cancer report encouraging oncologic outcomes and acceptable toxicity with SBRT. Mature results of phase III trials evaluating five-fraction SBRT regimens are eagerly awaited.

Structure guided deformable image registration for treatment planning CT and post stereotactic body radiation therapy (SBRT) Primovist® (Gd-EOB-DTPA) enhanced MRI.

The purpose of this study was to assess the performance of structure-guided deformable image registration (SG-DIR) relative to rigid registration and DIR using TG-132 recommendations. This assessment was performed for image registration of treatment planning computed tomography (CT) and magnetic resonance imaging (MRI) scans with Primovist® contrast agent acquired post stereotactic body radiation therapy (SBRT). SBRT treatment planning CT scans and posttreatment Primovist® MRI scans were obtained for 14 patients. The liver was delineated on both sets of images and matching anatomical landmarks were chosen by a radiation oncologist. Rigid registration, DIR, and two types of SG-DIR (using liver contours only; and using liver structures along with anatomical landmarks) were performed for each set of scans. TG-132 recommended metrics were estimated which included Dice Similarity Coefficient (DSC), Mean Distance to Agreement (MDA), Target Registration Error (TRE), and Jacobian determinant. Statistical analysis was performed using Wilcoxon Signed Rank test. The median (range) DSC for rigid registration was 0.88 (0.77-0.89), 0.89 (0.81-0.93) for DIR, and 0.90 (0.86-0.94) for both types of SG-DIR tested in this study. The median MDA was 4.8 mm (3.7-6.8 mm) for rigid registration, 3.4 mm (2.4-8.7 mm) for DIR, 3.2 mm (2.0-5.2 mm) for SG-DIR where liver structures were used to guide the registration, and 2.8 mm (2.1-4.2 mm) for the SG-DIR where liver structures and anatomical landmarks were used to guide the registration. The median TRE for rigid registration was 7.2 mm (0.5-23 mm), 6.8 mm (0.7-30.7 mm) for DIR, 6.1 mm (1.1-20.5 mm) for the SG-DIR guided by only the liver structures, and 4.1 mm (0.8-19.7 mm) for SG-DIR guided by liver contours and anatomical landmarks. The SG-DIR shows higher liver conformality as per TG-132 metrics and lowest TRE compared to rigid registration and DIR in Velocity AI software for the purpose of registering treatment planning CT and post-SBRT MRI for the liver region. It was found that TRE decreases when liver contours and corresponding anatomical landmarks guide SG-DIR.

Adherence to Treatment, Response and Patterns of Failure in Pediatric Parameningeal Rhabdomyosarcoma: Experience From a Tertiary Cancer Care Center From India.

The study was aimed at evaluating adherence to treatment protocol and outcome in pediatric parameningeal rhabdomyosarcoma (PM-RMS). We analyzed the characteristics, treatment administered, outcomes and patterns of failure of pediatric PM-RMS, who were treated with multimodality therapy between January 2005 and December 2013.Univariate and multivariate analysis (MVA) was completed to evaluate the impact of various prognostic factors. Thirty-seven patients were treated at our institution. Majority of them had the primary disease in paranasal sinuses (n=13). Majority of the patients belonged to group III (n=30) and stage III (n=24). The overall response rate to treatment was 52.5% (n=21). At a mean follow-up of 19.1 months, 23 patients developed disease progression. The actuarial rates of failure-free survival and overall survival (OS) at 2 years were 40% and 67.5%, respectively. Patients who received >20 weeks of intended chemotherapy schedule (P=0.02) and had complete response to first-line treatment (P=0.0004) were found to have superior failure-free survival on MVA. Complete response was the lone determinant of superior OS on MVA (P=0.006). Majority of patients with PM-RMS present with advanced stage disease. Response to first-line treatment is a significant predictor of superior progression-free survival and OS in these patients.

Supramolecular polyelectrolyte complex (SPEC): pH dependent phase transition and exploitation of its carrier properties.

A supramolecular poly-electrolyte complex (SPEC) comprising poly-electrolyte acrylic acid with supramolecularly complexed guanidium is reported. This complex shows pH responsive phase transitions, which are described and characterized using microscopy, spectroscopy, density functional theory studies and Monte Carlo simulations. The phase behaviour of the SPEC is exploited by loading a dye like perylene and a drug, viz., doxorubicin, and their pH dependent controlled release is demonstrated, owing to the pH dependent phase change of the SPEC.

Direct Observation of the Formation Pathway of [Mo132] Keplerates.

The formation pathway of a closed spherical cluster [Mo132], starting from a library of building blocks of molybdate anions, has been reported. Electrospray ionization mass spectrometry, Raman spectroscopy, and theoretical studies describe the formation of such a complex cluster from a reduced and acidified aqueous solution of molybdate. Understanding the emergence of such an enormous spherical model cluster may lead to the design of new clusters in the future. Formation of such a highly symmetric cluster is principally controlled by charge balance and the emergence of more symmetric structures at the expense of less symmetric ones.

Treatment outcome and patterns of failure in patients of non-pineal supratentorial primitive neuroectodermal tumor: review of literature and clinical experience form a regional cancer center in north India.

BACKGROUND: Supra-tentorial primitive neuroectodermal tumors (SPNET) are high-grade, hemispheric tumors, which account for around 2-3 % of pediatric brain tumors. We herein intend to report the clinical features and treatment outcome of patients with nonpineal SPNET treated at our institute. METHODS: Clinical data were collected by retrospective chart review from 2006 to 2012. Histopathology slides were reviewed, and relevant immunohistochemistry stains were done. Overall survival (OS), recurrence-free survival (RFS) and event-free survival (EFS) were analyzed by the Kaplan-Meier product-limit method. RESULTS: Fifteen patients met the study criterion (male: female = 2:1). Median age at presentation was 11 years (range 3-49 years). Surgical resection was gross total in 6 (40%) and subtotal in 8 (53.33%) patients. At presentation, two patients had leptomeningeal dissemination. Radiation therapy was delivered in 11 (73.33%) patients: craniospinal irradiation in 8 (36 Gy/20 fractions/4 weeks to the craniospinal axis followed by a local boost of 20 Gy/10 fractions/2 weeks) and focal RT in 3 patients. Systemic chemotherapy (median 6 cycles; range 1-16 cycles), given in 13 (86.67%) patients, included the VAC regimen (vincristine, adriamycin, cyclophosphamide) alternating with IE (ifosfamide,etoposide). After a median follow-up of 22.6 months (mean, 24.47 months), complete response and progressive disease were noted in 8 (53.33%) and 7 (46.67%) patients, respectively. Median OS was not reached, and estimated median EFS was noted to be 4.12 years (actuarial rate of EFS at 2 years, 55.2%). CONCLUSION: Maximal safe resection followed by craniospinal irradiation and systemic chemotherapy with 6-12 cycles of an alternating regimen of VAC and IE is a reasonable treatment strategy in patients with nonpineal SPNET.

Squamous cell carcinoma of larynx in an 8-year-old child: successful management with chemo-radiation.

Incidence of laryngeal squamous cell cancer (SCC) in childhood is rare, more so in children below 10 years of age. Due to the rarity of the disease and nonspecific symptoms diagnosis often gets delayed. Treatment is challenging and demands expert multi-modality care. We describe the clinico-pathologic findings and management of laryngeal cancer with chemo-radiation in an 8-year-old male. After 18 months of completion of treatment the child is in complete remission clinically and radiologically. This report aims at increasing awareness of head and neck SCC in paediatric population and also underscores the importance of multi-modality care in managing such cases.

Micropore engineering of carbonized porous aromatic framework (PAF-1) for supercapacitors application.

Micropore engineering of porous carbons on the effect of capacitance was explored using a carbonized porous aromatic framework (PAF-1). The porous carbons obtained through different carbonization methods show different pore structures enabling us to do this. The capacitance was measured both in aqueous electrolyte and different organic electrolytes. The porous carbons prepared by KOH activation show both high microporous volume, which is beneficial for charge storage, and mesoporous volume, which is devoted to fast ion diffusion in the pores; properties which are highly desirable. It shows a capacitance as high as 280 F g(-1) and 203 F g(-1) at a current density of 1 A g(-1) in 6.0 M KOH and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMImTFSI), respectively. We also demonstrate the effect of diffusion and that of geometric packing of the electrolyte ions in the pores, where a commensurate match of the electrolyte ions with the pores of carbonized materials control and influence significantly the capacitance of these materials.

Symptom Burden and Quality of Life in Advanced Head and Neck Cancer Patients: AIIMS Study of 100 Patients.

AIM: Head and neck cancers (HNCa) are the most common cancers among males in India and 70-80% present in advanced stage. The study aims to assess symptom burden and quality of life (QOL) in advanced incurable HNCa patients at presentation. MATERIALS AND METHODS: One hundred patients were asked to fill EORTC QLQ-C15-PAL questionnaire, which consisted of Global QOL, physical functioning (PF), emotional functioning (EF), fatigue (FA), nausea-vomiting (NV), pain (PA), dyspnea (DY), sleep (SL), appetite (AP), and constipation (CO). Additional questions pertaining to swallowing (SW), hoarseness (HO), cough (CG), weight loss (WL), using pain killers (PK), taste (TA), bleeding (BL), hearing (HE), pain in neck lump (PALMP), opening mouth (OM), and oral secretions (OS) were asked based on a modified EORTC-HN35 questionnaire. Scoring was according to EORTC scoring manual. Mean, median and range were calculated for each item for the entire cohort. RESULTS: The female:male ratio was 17:83.42% of them were ≥60 years of age. Sixty-six patients had T4, 25 had T3, 36 had N2, and 33 had N3 disease. Median QOL was 50 (range 0-83.33) and PF was 77.78 (0-100). Median score for EF and FA was 50. Median score for PA, PK, and SL was 66.67 while that for AP was 33.33. Median value for SW, HO, WL, BL, PALMP, OM, and OS was 33.33 (100-0) while TA, CG, NV, DY, and HE had a median score of 0.00. CONCLUSION: Advanced HNCa has a significant burden of symptoms. These results would help in giving patients better symptom directed therapies and improve their QOL.

Helical Tomotherapy versus Three-Dimensional Conformal Radiotherapy in High Risk Prostate Cancer: A Phase III Randomized Controlled Trial.

BACKGROUND: We present long-term outcomes from a phase III randomized controlled trial that compared helical tomotherapy with three-dimensional conformal radiotherapy (3D-CRT) in the treatment of high-risk prostate cancer (PCa). METHODS: Newly diagnosed patients with high-risk PCa were randomly allocated to receive radical radiotherapy using 3D-CRT or helical tomotherapy. In both arms, patients received an initial dose of 46 Gy in 23 fractions to the prostate and pelvic lymph nodes followed by additional boost to the prostate of 32 Gy in 16 fractions. Radiotherapy was combined with 3 years of adjuvant androgen deprivation. The primary endpoint was late (>90 days since RT initiation) rectal toxicity. RESULTS: Overall,123 patients were randomly assigned to either the 3D-CRT (n=60) or tomotherapy (n=63) arms. Median follow-up was 161 months. Overall, the proportion of patients with grade ≥2 late rectal toxicity was 8.3% (95% CI: 3.1 to 19.1; n=5) in the 3D-CRT arm and 11.1% (95% CI: 5.0 to 22.2; n=7) in the tomotherapy arm with no significant between-arm difference (p=0.83). There was no significant difference (p=0.17) in the proportion of patients with late grade ≥2 genitourinary toxicity:10.0% (95% CI: 4.1-21.2) in the 3D-CRT arm and 20.6% (95% CI: 11.9-33.0) in the tomotherapy arm. There was no significant difference in the hazard of biochemical progression or death between the two groups (HR for the tomotherapy arm: 0.72; 95% CI: 0.46-1.15, p=0.17). CONCLUSIONS: In this phase III trial, the overall incidence of grade ≥2 rectal toxicity was low and was not significantly different between the two arms. There was non-significant evidence of improved biochemical progression-free survival in patients treated with tomotherapy. These findings should be interpreted considering the possibility of type II errors due to limited sample size and low event rates. GOV IDENTIFIER: NCT00326638.

Multiparametric Magnetic Resonance Imaging- Guided Dose-Escalated Radiation Therapy for Localized Prostate Cancer: A Prospective Phase 2 Trial.

PURPOSE: This trial's purpose was to determine the late toxicity associated with dose escalation to Prostate Imaging Reporting and Data System (PI-RADS) III-V lesions on multiparametric magnetic resonance imaging (MRI) with an image guided combined IMRT-stereotactic body radiation therapy (SBRT) approach in men with localized prostate cancer. METHODS AND MATERIALS: In this phase 2 trial patients with localized prostate cancer with clinical tumor stage T1-T3bN0 and at least one PIRADS III-V lesion were recruited to receive 45 Gy in 25 fractions to the prostate and seminal vesicles followed by a boost of 18 Gy in 3 fractions to the prostate with a simultaneous integrated boost 21 Gy in 3 fractions to the PI-RADS lesion(s). The primary endpoint was the cumulative incidence of late grade ≥3 genitourinary and gastrointestinal toxicity by 18 months (National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). RESULTS: Overall, 50 patients were enrolled in this study, and 43 patients completed at least 18 months of follow-up. The cumulative incidence of grade 1, 2, and 3 late genitourinary toxicity at 18 months was 18%, 53%, and 2%. One patient was noted to have grade 3 hematuria and needed cystoscopy-guided cauterization. No acute grade 3 gastrointestinal or genitourinary toxicities were observed. The cumulative incidence of grade 1, 2, and 3 late gastrointestinal toxicity at 18 months was 31%, 4%, and 0%, respectively. At a median follow-up of 43.5 months, 3 patients developed biochemical recurrence, each with distant bone metastases without local or nodal recurrence. At 3 years, freedom from biochemical failure rate was 95.3% (95% CI, 89.2%-100%). CONCLUSIONS: Multiparametric MRI-guided dose escalation to PI-RADS III-V lesions using a combined image guided IMRT-SBRT approach is associated with an acceptable risk of late gastrointestinal and genitourinary toxicity. The results should be interpreted with caution considering their single institutional nature, small sample size, and short follow-up and should be validated in a larger study.