Hypofractionated re-irradiation with bevacizumab for relapsed chemorefractory glioblastoma after prior high dose radiotherapy: a feasible option for patients with large-volume relapse.

PURPOSE: There remains no standard of care for patients with recurrent and chemorefractory glioblastoma. Re-irradiation (reRT) provides an additional management option. However, published series predominantly focus on small reRT volumes utilizing stereotactic hypofractionated regimens. Concerns regarding toxicity have limited utilisation of reRT for larger recurrences, however this may be mitigated with use of bevacizumab (BEV). METHODS AND MATERIALS: A prospective database of patients managed with the EORTC-NCIC (Stupp) protocol 60 Gy chemoradiotherapy protocol for glioblastoma between 2007 and 2021 was reviewed for those patients receiving reRT for chemorefractory relapse. Serial MRI and PET were used to establish true progression and exclude patients with pseudoprogression or radionecrosis from reRT. The primary endpoint was overall survival (OS) from date of reRT. Prognostic factors were also assessed. RESULTS: 447 patients managed for glioblastoma under the Stupp protocol were identified, of which 372 had relapsed and were thus eligible for reRT. 71 patients underwent reRT. Median relapse-free survival from diagnosis for the reRT and overall cohorts were similar at 11.6 months (95%CI:9.4-14.2) and 11.8 months (95%CI:9.4-14.2) respectively. 60/71 (85%) reRT patients had received BEV prior to reRT and continued concurrent BEV during reRT. Of the 11 patients not managed with BEV during reRT, 10 required subsequent salvage BEV. ReRT patients were younger (median 53 vs. 59 years, p < 0.001), had better performance status (86% vs. 69% ECOG 0-1, p = 0.002) and more commonly had MGMT promoter-methylated tumours (54% vs. 40%, p = 0.083) compared to non-reRT patients. Median reRT PTV volume was 135cm3 (IQR: 69-207cm3). Median OS from reRT to death was 7.1 months (95%CI:6.3-7.9). Patients aged < 50, 50-70 and > 70 years had post-reRT median OS of 7.7, 6.4 and 6.0 months respectively (p = 0.021). Median post-reRT survival was longer for patients with ECOG performance status 0-1 compared to 2-3 (8.1 vs. 6.3 months, p = 0.039). PTV volume, site of relapse, MGMT promoter-methylation status and extent of initial surgical resection were not associated with post-reRT survival. ReRT was well-tolerated. Out of the 6 patients (8%) admitted to hospital after reRT, only one was for reRT toxicity. This was a CTCAE grade 3 radiation necrosis event in a patient managed without prior BEV. CONCLUSION: Patients with recurrent glioblastoma who have been previously treated with 60 Gy radiotherapy have a meaningful survival benefit from large volume re-irradiation which is well tolerated. ReRT should not be ignored as a salvage treatment option in patients with chemorefractory progressive disease.

Leptomeningeal neuraxis relapse in glioblastoma is an uncommon but not rare event associated with poor outcome.

BACKGROUND: Spinal neuraxis leptomeningeal metastasis (LM) relapse in glioblastoma is an uncommon event that is challenging to manage. This study aims to determine the incidence, associated factors, and outcome of LM relapse in patients with glioblastoma managed with radical intent. METHODS: Patients managed for glioblastoma using the EORTC-NCIC (Stupp) Protocol from 2007 to 2019 were entered into a prospective ethics-approved database. Follow-up included routine cranial MRI surveillance with further imaging as clinically indicated. LM relapse was determined by MRI findings and/or cerebrospinal fluid analysis. The chi-square test of independence was used to evaluate clinico-pathologic factors associated with increased risk of subsequent LM relapse. Median survival post-LM relapse was calculated using Kaplan-Meier technique. RESULTS: Four-hundred-and-seven patients were eligible, with median follow-up of 60 months for surviving patients. Eleven (2.7%) had LM at first relapse and in total 21 (5.1%) experienced LM in the entire follow-up period. Sites of LM relapse were 8 (38%) focal spinal, 2 (10%) focal brainstem medulla and 11 (52%) diffuse spinal. Median overall survival from initial diagnosis for the entire cohort was 17.6 months (95% CI 16.7-19.0). Median survival from LM relapse to death was 39 days (95% CI: 19-107). Factors associated with LM relapse were age less than 50 years (p < 0.01), initial disease located in the temporal lobe (p < 0.01) and tumours lacking MGMT promoter methylation (p < 0.01). CONCLUSIONS: LM relapse is an uncommon but not rare event in patients managed radically for glioblastoma. It is associated with poor outcome with the majority of patients deceased within two months of recognition.

Mapping of Local Recurrences After Radical Prostatectomy Using 68-Gallium-Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography: Implications for Postprostatectomy Radiation Therapy Clinical Target Volumes.

PURPOSE: Our objective is to describe the distribution of local recurrences after radical prostatectomy (RP) as delineated using 68-Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) to identify areas where current consensus guideline clinical target volumes (CTVs) are insufficient or excessive and to identify predictors of recurrence location within the fossa. METHODS AND MATERIALS: Retrospective review of databases from 2 tertiary referral centers was performed to identify patients who underwent 68Ga-PSMA PET/CT for biochemical recurrence after RP. Those with a component of local recurrence were included for further analysis. The epicenter of each recurrence was defined relative to reference points in 3 axes, categorized into 1 of 7 levels in the superior/inferior axis relative to the vesicourethral anastomosis, and recorded as within or outside the Faculty of Radiation Oncology Genito-urinary Group (FROGG) and Radiation Therapy Oncology Group consensus CTVs. Univariate and multivariate analysis was performed to identify predictors of recurrence location based on clinical and histopathologic variables. RESULTS: One thousand forty-nine 68Ga-PSMA PET/CT scans were reviewed. One hundred forty sites of local recurrence were identified on 132 scans. Relative to the vesicourethral anastomosis, 13 (9%), 31 (22%), 17 (12%), 24 (17%), 27 (19%), 20 (14%), and 8 (6%) recurrences occurred >5 mm inferior; within 5 mm above or below; and 6 to 15 mm, 16 to 25 mm, 26 to 35 mm, 36 to 45 mm, and >45 mm superiorly, respectively. Thirteen (9%) and 2 (1.4%) recurrences occurred beyond the FROGG and Radiation Therapy Oncology Group consensus CTVs, respectively, with all below the inferior CTV margin. CONCLUSIONS: In the largest study to date mapping local recurrences after RP in 3-dimensions, we provide several insights to inform future contouring guidelines; in particular, 9% of recurrences occurred inferior to the FROGG CTV.

Prostate adenocarcinoma with mucinous features - is it PSMA avid?

Mucinous prostate adenocarcinoma represents <0.1% of prostate cancers. To our knowledge, no previous report has described the 68 Ga-PSMA-PET characteristics of this entity at the primary site. We present a case of a fit 85-year-old with PSA 0.55 ng/mL and ISUP grade 4 acinar adenocarcinoma with mucinous features on biopsy. 68 Ga-PSMA-PET revealed an intensely avid primary lesion in the right prostate (SUVmax 10.9), concordant with biopsy findings and encompassing both the PI-RADS 5 lesion identified on MRI and a PI-RADS 1 lesion that presumably represented the mucinous component. The patient was treated with definitive radiotherapy to the prostate and lymph nodes with 6 months of androgen deprivation therapy.

Radiation oncology during COVID-19: Strategies to avoid compromised care.

The COVID-19 pandemic will present a range of challenges to radiation oncology departments. Early data suggest that cancer patients carry a higher than average, but still low absolute risk of hospitalization from COVID-19. The risk of severe events for those who are hospitalized however, is high. Resources for usual cancer care will likely be limited. Decisions to alter, delay or omit treatment during this period should consider both the risk of the cancer and of COVID-19 to the patient, as well as resource constraints. There is a need for departments to adapt with goals of maintaining an uninterrupted, high quality service and of minimizing compromise to oncologic care.

Outcomes for elderly patients 75 years and older treated with curative intent radiotherapy for mucosal squamous cell carcinomas of the head and neck.

BACKGROUND: Elderly patients with mucosal squamous cell carcinomas of the head and neck (mHNSCC) represent a challenging clinical dilemma. METHODS: A retrospective review was performed of patients ≥75 years, treated with curative-intent radiotherapy for mHNSCC in two quaternary Sydney hospitals between 2007 and 2017. RESULTS: Ninety-five patients met inclusion criteria. The median age was 79 years (75-94). Patients received radiotherapy alone (n = 24), concurrent chemoradiotherapy (n = 22), surgery and adjuvant radiotherapy (n = 45), or surgery with adjuvant chemoradiotherapy (n = 4). Median follow-up was 4.5 years, median overall survival (OS) was 3.8 years, and 2-year and 5-year OS were 56% and 43%, respectively. Eastern Cooperative Oncology Group performance status of ≥2 (P < .001) was a statistically significant predictor of reduced OS. Thirty-four patients (36%) required hospitalization, 5 (5%) did not complete radiotherapy, and 9 (9%) were feeding tube dependent beyond 6 months. CONCLUSIONS: Appropriately selected elderly patients can achieve durable outcomes from curative intent radiotherapy with acceptable treatment toxicity.

Emergency department presentations in early stage breast cancer patients receiving adjuvant and neoadjuvant chemotherapy.

(Neo)adjuvant chemotherapy for early stage breast cancer is associated with side-effects, resulting in increased emergency department (ED) presentations. Treatment-related toxicity can affect quality of life, compromise chemotherapy delivery and treatment outcomes, and increase healthcare use. We performed a retrospective study of ED presentations in patients receiving curative chemotherapy for early breast cancer to identify factors contributing to ED presentations. Of 102 patients, 39 (38%) presented to ED within 30 days of chemotherapy, resulting in 63 ED presentations in total. Most common reasons were non-neutropenic fever (17 presentations/27%), neutropenic fever (15/24%), pain (9/14%), drug reaction (6/10%) and infection (4/6%). Factors significantly associated with ED presentation were adjuvant chemotherapy timing compared to neoadjuvant timing (P = 0.031), prophylactic antibiotics (P = 0.045) and docetaxel-containing regimen (P = 0.018).

Planning magnetic resonance imaging for prostate cancer intensity-modulated radiation therapy: Impact on target volumes, radiotherapy dose and androgen deprivation administration.

AIMS: Magnetic resonance imaging (MRI) scans are increasingly utilized for radiotherapy planning to contour the primary tumors of patients undergoing intensity-modulated radiation therapy (IMRT). These scans may also demonstrate cancer extent and may affect the treatment plan. We assessed the impact of planning MRI detection of extracapsular extension, seminal vesicle invasion, or adjacent organ invasion on the staging, target volume delineation, doses, and hormonal therapy of patients with prostate cancer undergoing IMRT. METHODS: The records of 509 consecutive patients with planning MRI scans being treated with IMRT for prostate cancer between January 2010 and July 2012 were retrospectively reviewed. Tumor staging and treatment plans before and after MRI were compared. RESULTS: Of the 509 patients, 103 (20%) were upstaged and 44 (9%) were migrated to a higher risk category as a result of findings at MRI. In 94 of 509 patients (18%), the MRI findings altered management. Ninety-four of 509 patients (18%) had a change to their clinical target volume (CTV) or treatment technique, and in 41 of 509 patients (8%) the duration of hormone therapy was changed because of MRI findings. CONCLUSION: The use of radiotherapy planning MRI altered CTV design, dose and/or duration of androgen deprivation in 18% of patients in this large, single institution series of men planned for dose-escalated prostate IMRT. This has substantial implications for radiotherapy target volumes and doses, as well as duration of androgen deprivation. Further research is required to investigate whether newer MRI techniques can simultaneously fulfill staging and radiotherapy contouring roles.

Prevalence of complementary and alternative therapy use by cancer patients undergoing radiation therapy.

AIM: The use of complementary and alternative therapies (CAT) in oncology patients is increasing in incidence, with calls to routinely screen for their use. We introduced a screening tool as part of clinical care to identify CAT use. METHODS: We evaluated all patients who attended the radiation oncology outpatient clinic between December 2011 and July 2012, who had filled out the CAT screening tool, and evaluated types of CAT use, reasons for use and predictors of CAT usage. RESULTS: A total of 639 patients completed the CAT screening tool, which was 75% of eligible patients. There were 464 (72.6%) men and 175 (27.4%) women, with a mean age of 69.9 years (range 27-94 years). Prostate cancer was the predominant diagnosis (53.1%), followed by breast cancer (17.5%) and skin cancer (14.7%). Of these, 530 patients (82.9%) had used at least one therapy. Of the 530 patients using CAT, the most quoted reasons for use were to improve quality of life (42.6%), to boost the immune system and general health (33.6%), to increase energy levels (32.6%) and to live longer (28.9%). Of the 530 users, only 112 patients (21.1%) took CAT to help cure their cancer. Women were significantly more likely to use CAT, as were patients with breast cancer. CONCLUSIONS: The use of CAT in patients with cancer is prevalent and more frequent in our population than in other published studies. Few patients use CAT to improve their cancer cure, but rather use CAT for other reasons.

Improved outcomes with intensity modulated radiation therapy combined with temozolomide for newly diagnosed glioblastoma multiforme.

Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT) is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT) in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months). We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.