Image-guided dose-escalated intensity-modulated radiation therapy for prostate cancer: treating to doses beyond 78 Gy.

UNLABELLED: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? High doses of radiotherapy correspond to higher cure rates. Most radiation centers in the UK and Australia limit prescription doses to 74-78 Gy and do not use IGRT and IMRT for all patients. The combination of IGRT and IMRT can limit the rectum and bladder to low doses allowing doses above 78 Gy to be delivered, including pelvic lymph node treatment, with low side effects. This paper provides a detailed guide of planning technique and expected toxicity to enable implementation of similar dose escalated prostate programmes in other radiotherapy centres. OBJECTIVE: To determine the short-term side-effects of dose-escalated image-guided intensity-modulated radiation therapy (IG-IMRT) for the definitive treatment of prostate cancer. PATIENTS AND METHODS: Eligible patients were treated at doses >78 Gy and with definitive intent. Patients from a prospective database with International Prostate Symptom Score (IPSS) and Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE) toxicity were recorded weekly during treatment and at follow-up. RESULTS: In all, 101 patients were included, with doses ranging from 78.3 to 84 Gy (median = 79.3). The median (range) age was 71 (46-83) years; 60% received concurrent androgen deprivation and 35% had pelvic lymph node treatment. The median (range) IPSS at baseline, on treatment and at first follow-up were 7 (0-35), 15 (1-34) and 6 (0-30), respectively. The percentages of patients with grade 2 or higher toxicity during treatment, at 3 months and at 2 years were, respectively, 6.9%, 1% and 2% for gastrointestinal symptoms and 39%, 6.9% and 3% for genitourinary symptoms. There was no significant difference in gastrointestinal toxicity during treatment (P= 0.860) or at 3 months (P= 0.334) between patients with and without lymph node treatment. CONCLUSION: Doses >78 Gy delivered using daily image guidance and IMRT are well tolerated, and by 3 months short-term side-effects have normalized for the majority of patients.

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.

Radiotherapy for node-positive prostate cancer: 2019 Recommendations of the Australian and New Zealand Radiation Oncology Genito-Urinary group.

The management of node-positive prostate cancer is highly variable, with both locoregional and systemic treatment options available. With the increasing use of novel imaging techniques such as PSMA-PET and MRI, combined with the increasing use of surgery for high-risk prostate cancer, clinical and pathological regional nodal disease is being detected at a higher rate and at an earlier stage than previously. This creates a window for a potentially curative management approach. The role of radiotherapy including optimal radiation target volumes and dose, as well as the timing and duration of accompanying systemic therapy remains uncertain. At a workshop in 2017, the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group (FROGG) identified variations in the management of node-positive prostate cancer identified on primary staging or on histopathology at radical prostatectomy. FROGG reviewed the literature and developed a set of evidence-based recommendations on the appropriate investigation and management of clinically and pathologically node-positive prostate cancer. These recommendations encompass imaging techniques, radiation treatment target volumes and doses, as well as the use of androgen deprivation therapy.

A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or (125)I permanent implant.

PURPOSE: To compare the toxicity and biochemical outcomes of intensity-modulated radiation therapy (IMRT) and (125)I transperineal permanent prostate seed implant ((125)I) for patients with low-risk prostate cancer. METHODS AND MATERIALS: Between 1998 and 2004, a total of 374 low-risk patients (prostate-specific antigen < 10 ng/ml, T1c-T2b, Gleason score of 6 or less, and no neoadjuvant hormones) were treated at Fox Chase Cancer Center (216 IMRT and 158 (125)I patients). Median follow-up was 43 months for IMRT and 48 months for (125)I. The IMRT prescription dose ranged from 74-78 Gy, and (125)I prescription was 145 Gy. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was recorded by using a modified Radiation Therapy Oncology Group scale. Freedom from biochemical failure was defined by using the Phoenix definition (prostate-specific antigen nadir + 2.0 ng/ml). RESULTS: Patients treated by using IMRT were more likely to be older and have a higher baseline American Urological Association symptom index score, history of previous transurethral resection of the prostate, and larger prostate volumes. On multivariate analysis, IMRT was an independent predictor of lower acute and late Grade 2 or higher GU toxicity and late Grade 2 or higher GI toxicity. Three-year actuarial estimates of late Grade 2 or higher toxicity were 2.4% for GI and 3.5% for GU by using IMRT compared with 7.7% for GI and 19.2% for GU for (125)I, respectively. Four-year actuarial estimates of freedom from biochemical failure were 99.5% for IMRT and 93.5% for (125)I (p = 0.09). CONCLUSIONS: The IMRT and (125)I produce similar outcomes, although IMRT appears to have less acute and late toxicity.

Radiotherapy for recurrent prostate cancer: 2018 Recommendations of the Australian and New Zealand Radiation Oncology Genito-Urinary group.

The management of patients with biochemical, local, nodal, or oligometastatic relapsed prostate cancer has become more challenging and controversial. Novel imaging modalities designed to detect recurrence are increasingly used, particularly PSMA-PET scans in Australia, New Zealand and some European countries. Imaging techniques such as MRI and PET scans using other prostate cancer-specific tracers are also being utilised across the world. The optimal timing for commencing salvage treatment, and the role of local and/or systemic therapies remains controversial. Through surveys of the membership, the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group (FROGG) identified wide variation in the management of recurrent prostate cancer. Following a workshop conducted in April 2017, the FROGG management committee reviewed the literature and developed a set of recommendations based on available evidence and expert opinion, for the appropriate investigation and management of recurrent prostate cancer. These recommendations cover the role and timing of post-prostatectomy radiotherapy, the management of regional nodal metastases and oligometastases, as well as the management of local prostate recurrence after definitive radiotherapy.

What dose of external-beam radiation is high enough for prostate cancer?

PURPOSE: To quantify the radiotherapy dose-response of prostate cancer, adjusted for prognostic factors in a mature cohort of men treated relatively uniformly at a single institution. PATIENTS AND METHODS: The study cohort consisted of 1,530 men treated with three-dimensional conformal external-beam radiotherapy between 1989 and 2002. Patients were divided into four isocenter dose groups: <70 Gy (n = 43), 70-74.9 Gy (n = 552), 75-79.9 Gy (n = 568), and > or =80 Gy (n = 367). The primary endpoints were freedom from biochemical failure (FFBF), defined by American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (nadir + 2.0 ng/mL) criteria, and freedom from distant metastases (FFDM). Multivariate analyses were performed and adjusted Kaplan-Meier estimates were calculated. Logit regression dose-response functions were determined at 5 and 8 years for FFBF and at 5 and 10 years for FFDM. RESULTS: Radiotherapy dose was significant in multivariate analyses for FFBF (ASTRO and Phoenix) and FFDM. Adjusted 5-year estimates of ASTRO FFBF for the four dose groups were 60%, 68%, 76%, and 84%. Adjusted 5-year Phoenix FFBFs for the four dose groups were 70%, 81%, 83%, and 89%. Adjusted 5-year and 10-year estimates of FFDM for the four dose groups were 96% and 93%, 97% and 93%, 99% and 95%, and 98% and 96%. Dose-response functions showed an increasing benefit for doses > or =80 Gy. CONCLUSIONS: Doses of > or =80 Gy are recommended for most men with prostate cancer. The ASTRO definition of biochemical failure does not accurately estimate the effects of radiotherapy at 5 years because of backdating, compared to the Phoenix definition, which is less sensitive to follow-up and more reproducible over time.

Multileaf Collimator Tracking Improves Dose Delivery for Prostate Cancer Radiation Therapy: Results of the First Clinical Trial.

PURPOSE: To test the hypothesis that multileaf collimator (MLC) tracking improves the consistency between the planned and delivered dose compared with the dose without MLC tracking, in the setting of a prostate cancer volumetric modulated arc therapy trial. METHODS AND MATERIALS: Multileaf collimator tracking was implemented for 15 patients in a prostate cancer radiation therapy trial; in total, 513 treatment fractions were delivered. During each treatment fraction, the prostate trajectory and treatment MLC positions were collected. These data were used as input for dose reconstruction (multiple isocenter shift method) to calculate the treated dose (with MLC tracking) and the dose that would have been delivered had MLC tracking not been applied (without MLC tracking). The percentage difference from planned for target and normal tissue dose-volume points were calculated. The hypothesis was tested for each dose-volume value via analysis of variance using the F test. RESULTS: Of the 513 fractions delivered, 475 (93%) were suitable for analysis. The mean difference and standard deviation between the planned and treated MLC tracking doses and the planned and without-MLC tracking doses for all 475 fractions were, respectively, PTV D99% -0.8% ± 1.1% versus -2.1% ± 2.7%; CTV D99% -0.6% ± 0.8% versus -0.6% ± 1.1%; rectum V65% 1.6% ± 7.9% versus -1.2% ± 18%; and bladder V65% 0.5% ± 4.4% versus -0.0% ± 9.2% (P<.001 for all dose-volume results). CONCLUSION: This study shows that MLC tracking improves the consistency between the planned and delivered doses compared with the modeled doses without MLC tracking. The implications of this finding are potentially improved patient outcomes, as well as more reliable dose-volume data for radiobiological parameter determination.

Health-related quality of life using intensity-modulated radiation therapy for post-prostatectomy radiotherapy.

INTRODUCTION: Post-prostatectomy radiotherapy (PPRT) with intensity-modulated radiation therapy (IMRT) has the potential to decrease toxicity by reducing dose to surrounding structures. We assessed its impact on health-related quality of life (HRQoL). METHODS: PPRT patients were enrolled in a prospective HRQoL database. To be eligible, patients were required to be treated with IMRT and have a minimum of 15-month follow up. HRQoL was assessed at baseline, 3, 9 and 15-24 months using the Expanded Prostate Cancer Index Composite questionnaire. Higher scores reflected better HRQoL. Results were analysed as both population means and as individual scores where a moderate change was 10-20 points and a substantial change was >20 points. RESULTS: There were 64 patients eligible and 83% of the cohort received salvage radiotherapy. Prescribed dose was 64 Gy in 32 fractions for adjuvant and 66 Gy in 33 fractions for salvage IMRT. Mean function scores for urinary, bowel and sexual domains were similar at baseline and 15 months (83.5, 94.2 and 16.9 vs. 82.2, 93.1 and 14.3, respectively). Mean global physical functioning (51.0 vs. 48.1) and mental functioning (51.6 vs. 54.2) showed no difference over time. Individual patient scores by 2 years showed a >20-point deterioration in urinary (12.5%), bowel (1.6%), sexual function (9.4%), physical functioning (3.1%) and mental functioning (1.6%). CONCLUSION: This report on HRQoL following post-prostatectomy IMRT demonstrates no variation in mean scores in any domain and only 1.6% of patients reporting a greater than 20-point deterioration between baseline and 15-24 months in bowel function.

An intraoperative real-time sleeved seed technique for permanent prostate brachytherapy.

PURPOSE: To describe a novel technique that integrates customized sleeved seed production to reduce seed migration using preloaded needles with real-time intraoperative dosimetric planning for patients treated with iodine-125 (I-125) permanent prostate seed implants. METHODS AND MATERIALS: Customized seed-spacer sequences were calculated for patients in real time based on an intraoperative transrectal ultrasound-guided volume study. Using a Fox Chase Cancer Center modified Best Iodine-125 seed loader (Best Medical, Springfield, VA), the seeds and spacers were inserted into a hollow suture material (sleeve) and then loaded into the implant needles. Needles were placed sequentially under transrectal ultrasound guidance with sagittal plane visualization of the dropped sleeved seeds. RESULTS: This technique was successfully implemented allowing intraoperative planning to be combined with real-time sleeved seed production. CONCLUSIONS: The use of sleeves for seeds combined with real-time intraoperative planning allowed for the intraoperative customization of implants with the practical advantages of linked seeds.

Radiation-induced tumor after stereotactic radiosurgery for an arteriovenous malformation: case report.

OBJECTIVE: To present a rare case of a radiation-induced malignancy after stereotactic radiosurgery. CLINICAL PRESENTATION: A 34-year-old woman presented with headaches. Imaging studies demonstrated a 4.5-cm arteriovenous malformation located in the pineal region. She was treated with a two-isocenter plan to a total dose of 1500 cGy prescribed to the 70% isodose line. She was lost to follow-up and presented with a change in mental status, nausea, headaches, and a generalized seizure 9 years later. Magnetic resonance imaging scans demonstrated a large, heterogeneously enhancing mass partially in the treatment volume. INTERVENTION: Surgical debulking demonstrated an infiltrating glial neoplasm consistent with a glioblastoma multiforme. There was no staining for epidermal growth factor receptor, whereas greater than 75% of nuclei stained positively with p53. CONCLUSION: The risk of radiation-induced tumors is currently unknown but needs to be determined to assess the risk-benefit profile for each patient.

Role of radiotherapy in ductal (endometrioid) carcinoma of the prostate.

BACKGROUND: Ductal carcinoma of the prostate is a rare variant of prostate cancer that presents most commonly with obstructive urinary symptoms or hematuria. This case series of 6 patients is the first to report the outcome of ductal carcinoma treated with external beam radiotherapy. METHODS: A retrospective review was performed of patients treated between 1980 and 2006 at Fox Chase Cancer Center, Philadelphia, Penn. Six patients were identified with ductal carcinoma. RESULTS: Five of the 6 patients were treated definitively and the sixth patient was treated at recurrence 3 years after a radical prostatectomy. Patient ages ranged from 66-80 years and the initial prostate-specific antigen (iPSA) ranged from 1.69-100.3 ng/mL. Three patients had a mixed acinar and ductal carcinoma, 2 with a Gleason score (GS) of 8 and 1 with a GS of 7. Of the patients treated definitively, 4 had clinical stage T2A-T2C and 1 had clinical stage T1B. Definitive radiotherapy was delivered to the prostate with doses between 72 Gy and 78 Gy. Pelvic lymph nodes were treated in all patients. One patient was treated postradical prostatectomy to the prostate bed to a dose of 60 Gy. Adjuvant androgen deprivation was given in 5 of the patients. Two of the patients died from metastatic disease at 1.4 and 7.1 years after treatment. The remaining 4 patients remain alive between 3.2 and 4.8 years from treatment, with 3 patients biochemically without evidence of disease. No patients have developed a local recurrence. CONCLUSIONS: Ductal carcinoma of the prostate may be treated effectively with external beam radiotherapy. Aggressive management is indicated, even with low-volume metastatic disease.