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Purpose: As a means of limiting normal tissue toxicity, proton-beam therapy (PBT) is an emerging radiation modality for glioblastoma (GBM) reirradiation. However, data for recurrent GBM treated with PBT reirradiation is limited. Therefore, we analyzed treatment patterns, toxicities, and clinical outcomes of patients with recurrent GBM treated with PBT reirradiation using the multi-institutional Proton Collaborative Group registry. Methods and Materials: Prospectively collected data for patients with recurrent GBM who underwent PBT while enrolled in Proton Collaborative Group study 01-009 (NCT01255748) were analyzed. We evaluated overall survival (OS), progression-free survival (PFS), and toxicity. Toxicities were scored per the Common Terminology Criteria for Adverse Events, version 4.0. Descriptive statistics were used to report patient, tumor, and treatment characteristics. Multivariable analyses (MVA) for toxicity were conducted using logistic regression. The Kaplan-Meier method was used to calculate OS and PFS. MVA for OS and PFS was conducted using Cox proportional-hazards models. The SAS statistical software was used for the analysis. Results: We identified 45 recurrent patients with GBM who underwent PBT reirradiation between 2012 and 2018. The median time between initial GBM diagnosis and recurrence was 20.2 months. The median follow-up time from PBT reirradiation was 10.7 months. Median PFS was 13.9 months (95% confidence interval [CI], 8.23-20.0 months) and median OS was 14.2 months (95% CI, 9.6-16.9 months) after PBT reirradiation. One patient experienced an acute grade 3 toxicity, 4 patients experienced late grade 3 toxicity (no grade ≥4 toxicities). MVA revealed that prior surgery was associated with a 91.3% decreased hazard of death (hazard ratio: 0.087; 95% CI, 0.02-0.42; P < .01). No explanatory variables were associated with PFS or grade 3 toxicities. Conclusions: This is the largest series to date reporting outcomes for PBT reirradiation of patients with recurrent GBM. Our analysis indicates that PBT is well tolerated and offers efficacy rates comparable with previously reported photon reirradiation.

Purpose: Total scalp irradiation (TSI) is used to treat malignancies of the scalp and face, including angiosarcomas, nonmelanoma skin cancers, and cutaneous lymphomas. Owing to the irregularity of the scalp contour and the presence of underlying critical organs at risk (OARs), radiation planning is challenging and technically difficult. To address these complexities, several different radiation therapy techniques have been used. These include the combined lateral photon-electron technique (3DRT), intensity-modulated radiation therapy (IMRT)/volumetric arc therapy (VMAT), helical tomotherapy (HT), and mold-based high-dose-rate brachytherapy (HDR BT). However, the use of proton radiation therapy (PRT) has never been documented. Materials and Methods: A 71-year-old, immunosuppressed man presented with recurrent nonmelanoma skin cancer of the scalp. He was successfully treated at our center with PRT to deliver TSI. A comparative VMAT treatment plan was generated and dose to critical OARs was compared. Results: We present the first clinical case report of PRT for TSI and dosimetric comparison to a VMAT plan. The PRT and VMAT plans provided equivalent target volume coverage; however, the PRT plan significantly reduced dose to the brain, hippocampi, and optical apparatus. Conclusion: TSI planned with PRT is relatively straightforward from a planning perspective and does not require a bolus. It also has the potential to decrease radiation therapy–related toxicity. However, PRT is relatively expensive and not universally available. The uncertainty surrounding the end-range of the proton beam is a consideration. Although there are potential disadvantages to using PRT for TSI, its use should be considered by treating radiation oncologists and referring physicians.

At present, the strongest evidence for the use of PET/computed tomography (CT) in gastrointestinal (GI) malignancies is to rule out distant metastatic disease at diagnosis, radiation treatment planning for anal malignancies, and disease recurrence monitoring in colorectal and anal malignancies. Use of PET/CT for GI malignancies continues to evolve over time, with new studies evaluating prognostic abilities of PET/CT and with increasing sensitivity and spatial resolution of more modern PET/CT scanners. The authors encourage future applications and prospective evaluation of the use of PET/CT in the staging, prognostication, and recurrence prediction for GI malignancies.

The use of biphasic cuirass ventilator supported radiation therapy has never been documented. We present the first technical report here. A 57-year-old man with obstructive sleep apnea presented with a T0N1M0 right sided, human papillomavirus related head and neck cancer diagnosed on excisional lymph node biopsy. On further workup, the cancer was found to have originated in the right tonsil and was staged as T1N1. The patient started definitive treatment with concurrent chemo-radiation therapy, but after 5 treatments was no longer able to lay in a supine position for treatment. Diagnostic imaging workup eventually revealed an idiopathic right sided hemi-diaphragm eventration. After consultation with cardiology, pulmonology, and head and neck surgery, recommendation was made for tracheostomy to tolerate supine radiotherapy position, but the patient refused. Instead, computed tomography simulation for radiotherapy replanning was performed using a combination of biphasic cuirass ventilation, home continuous positive airway pressure and oxygen. The patient then tolerated definitive treatment to a dose of 69.96 Gray in 33 fractions with concurrent chemotherapy and experienced no unexpected side effects. Although complex, daily treatment setup was consistent. Daily onboard imaging was precise and accurate. The patient continues to follow up with radiation oncology, medical oncology, and pulmonology. This is the first use of biphasic cuirass ventilator supported radiotherapy reported in the scientific literature. Although daily treatment setup is complex, its use could be considered in patients unable to tolerate radiation therapy treatment positioning as an alternative to tracheostomy.

Background Patients with locally advanced colon cancer (LACC) treated with surgery had a high risk of local recurrence. The outcomes can vary significantly among patients with pT3 disease. This study was undertaken to assess whether low-energy electronic intraoperative radiotherapy (eIORT) can achieve promising results comparing with electron beam IORT (IOERT) and whether specific subgroups of patients with pT3 colon cancer may benefit from eIORT. Methods We retrospectively reviewed 44 patients with pT3 LACC treated with eIORT. Clinicopathologic characteristics were analyzed to identify patients that could potentially benefit from eIORT. Kaplan-Meier survival analysis was used to assess overall survival (OS) and progression free survival (PFS). The log-rank test was used for the subgroup comparison. Results The median follow-up of patients was 20.5 months (range, 6.1–38.8 months). At the time of analysis, 38 (86%) were alive and 6 (14%) had died of their disease. The 3-year Kaplan-Meier of PFS and OS for the entire cohort were 82.8% and 82.1%, respectively. At median follow-up, no in-field failure within the eIORT field had occurred. Locoregional and distant failure had occurred in 2 (5%) patients each. The rate of perioperative 30-day mortality was 0% and morbidity rate was 11%. Five patients experienced 7 complications, including 4 early complications (30-d) and three late complications (>30 days) leading early and late morbidity rates of 9% and 7%, respectively. Conclusion Low-energy eIORT can be considered as part of management in pT3 LACC.

Additional file 1: Supplementary Table 1. The correlation r values of OS and PFS with disease factors.

This study is designed to investigate the mechanisms underlying effects of receptor tyrosine kinase(s) on androgen receptor (AR) in castrate resistant prostate cancer (CRPC). Hormone ablation therapies remain the mainstay of treatment for metastatic prostate cancer, but disease eventually reoccurs as CRPC where AR has been reactivated despite castrate androgen levels. Amongst ways that facilitate restoration of AR activity in CRPC, receptor tyrosine kinases (RTKs) have been reported to activate AR and induce CRPC growth through as of yet unclear mechanisms. Our investigative studies revealed that lapatinib (inhibits Her2/Her3 heterodimer and EGFR) treatment inhibited endogenous AR expression and activity in C4-2 CRPC cells. Lapatinib induced destabilization and proteosomal degradation of the AR with minimal effect on AR mRNA transcript levels. To further investigate if this effect was dependent on Her2/Her3 or EGFR, an EGFR inhibitor erlotinib was used. It produced modest effects on AR, indicating that effects of lapatinib are predominantly through Her2/Her3. As AKT, a serine/threonine kinase, functions downstream of Her2/Her3, we then directly investigated the effects of AKT on AR in CRPC cells. Our studies revealed that inhibition of AKT decreased endogenous AR expression through proteosomal degradation. Moreover AKT inhibition decreased endogenous AR activity and C4-2 cell survival, indicating that AKT positively regulates AR and CRPC growth. As many groups have previously reported conflicting effects of AKT on AR, we are now focused on the molecular basis for this positive effect of AKT on AR expression and function in CRPC. Preliminary studies indicate that AKT inhibition may be decreasing levels of heat shock proteins (Hsp70, Hsp90) that serve as chaperones for cytoplasmic AR, and may by another mechanism be decreasing AR accumulation in the nucleus. We anticipate that these studies will provide a clear mechanistic view of effects of RTKs and AKT on AR in CRPC and highlight molecules that may be targeted for novel therapeutic interventions. Citation Format: Ankur Sharma, Steven P. Balk. Receptor tyrosine kinase(s) modulate androgen receptor signaling in castrate-resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C3.