Differences in real-world outcomes by risk classification for localized prostate cancer patients after radiation therapy.

BACKGROUND: Limited real-world evidence exists on the long-term clinical outcomes of patients with localized prostate cancer (LPC) who received external beam radiation therapy (EBRT) as the initial treatment. This study evaluated clinical outcomes of US patients with high-risk LPC (HR-LPC) and low/intermediate-risk LPC (LIR-LPC) who received EBRT. METHODS: This retrospective study using Surveillance, Epidemiology, and End Results-Medicare linked data from 2012 to 2019 included patients ≥ 65 years old who received EBRT as initial therapy. Baseline patient characteristics were summarized, metastasis-free survival (MFS), overall survival, and time to initiation of advanced prostate cancer treatment were compared using Kaplan-Meier (KM) and adjusted Cox proportional hazard (PH) models. 5-year survival probabilities stratified by race/ethnicity (non-Hispanic [NH] White, NH Black, NH Asian, and Hispanic) were assessed. RESULTS: Of 11,313 eligible patients, 41% (n = 4600) had HR-LPC and 59% (n = 6713) had LIR-LPC. Patient characteristics for both groups were comparable, with mean age at EBRT initiation > 70 years, 86% white, and mean follow-up time >40 months. More patients in the HR-LPC than LIR-LPC groups (78% vs 34%) had concurrent androgen deprivation therapy use and for a longer duration (median 10.4 months vs. 7.4 months). A higher proportion of HR-LPC patients developed metastasis, died, or received advanced prostate cancer treatment. Adjusted Cox PH survival analyses showed significantly (p < 0.0001) higher risk of mortality (hazard ratios [HR], 1.57 [1.38, 2.34]), metastasis or death (HR, 1.97 [1.78, 2.17]), and advanced prostate cancer therapy use (HR, 2.57 [2.11, 3.14]) for HR-LPC than LIR-LPC patients. Within 5 years after the initial EBRT treatment, 18%-26% of patients with HR-LPC are expected to have died or developed metastasis. The 5-year MFS rate in the HR-LPC group was lower than the LIR-LPC group across all racial/ethnic subgroups. NH Black patients with HR-LPC had the highest all-cause mortality rate and lowest rate of receiving advanced prostate cancer treatment, compared to other racial/ethnic subgroups. CONCLUSIONS: This real-world study of clinical outcomes in patients with LPC treated with EBRT suggests substantial disease burden in patients with HR-LPC and highlights the need for additional treatment strategies to improve clinical outcomes in patients with HR-LPC.

Focal radiotherapy boost to MR-visible tumor for prostate cancer: a systematic review.

PURPOSE: The FLAME trial provides strong evidence that MR-guided external beam radiation therapy (EBRT) focal boost for localized prostate cancer increases biochemical disease-free survival (bDFS) without increasing toxicity. Yet, there are many barriers to implementation of focal boost. Our objectives are to systemically review clinical outcomes for MR-guided EBRT focal boost and to consider approaches to increase implementation of this technique. METHODS: We conducted literature searches in four databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline. We included prospective phase II/III trials of patients with localized prostate cancer underdoing definitive EBRT with MR-guided focal boost. The outcomes of interest were bDFS and acute/late gastrointestinal and genitourinary toxicity. RESULTS: Seven studies were included. All studies had a median follow-up of greater than 4 years. There were heterogeneities in fractionation, treatment planning, and delivery. Studies demonstrated effectiveness, feasibility, and tolerability of focal boost. Based on the Phoenix criteria for biochemical recurrence, the reported 5-year biochemical recurrence-free survival rates ranged 69.7-100% across included studies. All studies reported good safety profiles. The reported ranges of acute/late grade 3 + gastrointestinal toxicities were 0%/1-10%. The reported ranges of acute/late grade 3 + genitourinary toxicities were 0-13%/0-5.6%. CONCLUSIONS: There is strong evidence that it is possible to improve oncologic outcomes without substantially increasing toxicity through MR-guided focal boost, at least in the setting of a 35-fraction radiotherapy regimen. Barriers to clinical practice implementation are addressable through additional investigation and new technologies.

Intensity-modulated radiation therapy for intermediate-risk prostate cancer: does ADT still have an impact in the dose-escalated external beam radiation therapy era?

BACKGROUND: This study aimed to investigate the effect of androgen deprivation therapy (ADT) on the survival of intermediate-risk prostate cancer (IR-PCA) patients treated with dose-escalated external beam radiation therapy (DE-EBRT), and to determine the group that will benefit from ADT. METHODS: We analysed 620 IR-PCA patients treated with DE-EBRT at two institutions. Variables were adjusted using the stabilised inverse probability of treatment weighting method (sIPTW) between radiation therapy (RT) and RT plus ADT groups. Biochemical relapse-free survival (bRFS) rate and overall survival (OS) rate were compared using Kaplan-Meier analysis and log-rank test. Cox proportional hazard analysis (CPH) was conducted to detect unfavorable risk factors. RESULTS: This study included 405 patients; with 217 and 188 patients in the RT and RT plus ADT groups, respectively. The prescribed radiation dose was 78 Gy in 39 fractions. The median follow-up time was 82.0 months. After sIPTW-adjustment, 214.3 and 189.7 patients were assigned to the RT and RT plus ADT groups, respectively. The 7-year bRFS and OS were 89.3% and 94.6% in RT group and 92.3% and 91.0% in RT plus ADT group, respectively. Before and after sIPTW adjustment, no statistically significant differences were found in these endpoints between treatment groups. Multivariate CPH for bRFS revealed Gleason score (GS) 4 + 3 as an unfavorable risk factor, and ADT improved biochemical control of them. CONCLUSION: ADT may not always be effective in all Japanese IR-PCA patients treated with DE-EBRT, but it can improve biochemical control in patients with GS 4 + 3.

Upper limit of radiation treatment portals in rectal cancer: is it wise to keep using bony landmarks in the present era of 3D conformal treatment?

Background: This study aimed to compare the levels of L5-S1 interspace and the bifurcation of common iliac vessels on simulation images of rectal cancer patients to evaluate the adequacy of superior borders in conventional 2D planning for covering internal iliac vessels. Materials and methods: Simulation images of 236 rectal cancer patients who received neoadjuvant chemoradiation and surgery were analyzed. The images were retrieved from the radiation treatment database and included delineations of L5-S1 interspace and common iliac vessel bifurcation. Distances between these landmarks were measured. Results: Among the 236 patients, the majority had the common iliac artery bifurcation positioned above the L5-S1 interspace. Specifically, 78.3% of patients had the right common iliac bifurcation above L5-S1 interspace, with an average distance of 2.02 cm. For the left common iliac artery, 77.11% of patients had the bifurcation above L5-S1 interspace, with an average distance of 1.99 cm. Notably, there were cases where the bifurcations were not at the same level. Conclusion: Using the L5-S1 junction as the upper border of the treatment portal may result in missing proximal nodes at risk of metastases. However, further research is needed to determine the significance of failures above the L5-S1 interspace for justifying the inclusion of the common iliac artery bifurcation in the treatment portal.

Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms (SPORTSMEN): a randomized phase II study protocol.

Background: Approximately 40% of patients with metastatic cancer will have spinal metastatic disease. Historically treated with external beam radiation therapy (EBRT) with limited durability in pain control, the increased lifespan of this patient population has necessitated more durable treatment results via spine radiosurgery/stereotactic body radiation therapy (SBRT). The goal of this study is to assess three-month pain freedom rates via the Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms (SPORTSMEN) randomized trial. Materials and methods: This study is a prospective randomized three-arm phase II trial which will recruit patients with symptomatic spine metastases. All patients will be randomized to standard-of care SBRT (24 Gy in 2 fractions), single-fraction SBRT (19 Gy in 1 fraction), or EBRT (8 Gy in 1 fraction), with the primary endpoint of three-month pain freedom (using the Brief Pain Inventory). We expect that SPORTSMEN will help definitively answer the efficacy of spine SBRT versus EBRT for achieving pain freedom, while defining the safety and efficacy of 19 Gy single-fraction spine SBRT. Local control will be defined according to Spine Response Assessment in Neuro-Oncology (SPINO) criteria. Discussion: This is the first phase II trial to objectively assess optimal spine SBRT dosing in the treatment of symptomatic spine metastatic disease, while assessing spine SBRT versus EBRT. Findings should allow for better determination of the efficacy of two-fraction spine SBRT versus EBRT in the United States, as well as for the novel single-fraction 19 Gy spine SBRT regimen in patients with symptomatic spine metastases. Trial Registration: Clinicaltrials.gov identifier: NCT05617716 (registration date: November 14, 2022).

Comparative oncological outcomes after radical prostatectomy or external beam radiation therapy plus androgen deprivation therapy in men with clinical T3b prostate cancer.

OBJECTIVE: To compare oncological outcomes in men with clinical T3b prostate cancer who underwent radical prostatectomy or a combination of radiation therapy plus androgen deprivation therapy. METHODS: Men with clinical T3b prostate cancer who underwent radical prostatectomy or radiation therapy plus androgen deprivation therapy between 2007 and 2014 were evaluated. All patients were relatively healthy, with Eastern Cooperative Oncology Group performance status of 0 or 1 without nodal or distant metastasis. Cancer-specific survival was analyzed. Age, Charlson Comorbidity Index, biopsy Gleason score and pretreatment prostate-specific antigen were adjusted by propensity score matching. The Cox proportional hazards model was used to assess factors prognostic of cancer-specific survival. RESULTS: Of the 152 patients with clinical T3b prostate cancer, 45 underwent radical prostatectomy, and 107 underwent radiation therapy plus androgen deprivation therapy between 2007 and 2014. The mean cancer-specific survival was significantly longer in the radical prostatectomy than in the radiation therapy plus androgen deprivation therapy group (P = 0.029). Age, Charlson Comorbidity Index and pretreatment prostate-specific antigen were significantly higher in the radiation therapy plus androgen deprivation therapy group. In the propensity score matched population of 24 patients each, the median cancer-specific survival remained significantly longer in the radical prostatectomy than in the radiation therapy plus androgen deprivation therapy group (not reached vs 112.93 ± 11.94 months, P = 0.026). Multivariate analysis showed that undergoing radiation therapy plus androgen deprivation therapy was the only significant poor prognostic factor for cancer-specific survival (hazard ratio 6.694, 95% confidence interval 1.642-27.592, P = 0.008). CONCLUSION: Cancer-specific survival was significantly longer in men with clinical T3b prostate cancer who underwent radical prostatectomy than radiation therapy plus androgen deprivation therapy, suggesting that radical prostatectomy can be a better treatment option for the initial definitive treatment for these patients.

A feasibility study of a modified treatment strategy combined external beam radiation therapy and brachytherapy for cervical cancer.

PURPOSE: To evaluate the feasibility of a modified treatment strategy combined external beam radiation therapy (EBRT) and brachytherapy (BT) for cervical cancer through a dosimetry analysis. MATERIAL AND METHODS: This study retrospectively selected 12 cervical cancer patients treated with the conventional treatment strategy, which consisted of 45─50 Gy/25 fractions of EBRT using volumetric-modulated arc therapy (VMAT) and image-guided BT with a fraction dose of 5─7 Gy. The modified treatment strategy decreased the central EBRT dose while increasing the number of BT fractions. New target volumes were additionally contoured, and new VMAT EBRT plans were generated for the modified treatment strategy. The dosimetric parameters for evaluation included the doses to the most irradiated 2 cc (D2cc) of the organs at risk (OARs) and doses to at least 90% (D90) of the gross tumor volume (GTV) and high-risk clinical target volume (HR-CTV). The total doses to OARs and targets obtained by adding the equivalent doses in 2 Gy fraction (EQD2) from the EBRT and BT plans were used for quantitative comparison between the modified and conventional treatment strategies. RESULTS: Comparison to the conventional treatment strategy, the modified treatment strategy resulted in a higher bladder D2cc, a slightly lower rectal D2cc and a similar HR-CTV D90, all with no significant differences (p > 0.05). The GTV D90 of the modified treatment strategy was significantly higher than that of the conventional treatment strategy (p < 0.01). CONCLUSION: The modified treatment strategy can significantly increase the BT dose while remaining the total doses to the bladder and rectum basically unchanged, demonstrating its feasibility and promising prospect in clinical use.

An evaluation of quality assurance guidelines comparing the American College of Radiology and American Association of Physicists in Medicine task group 284 for magnetic resonance simulation.

PURPOSE: The purpose of this study was to evaluate similarities and differences in quality assurance (QA) guidelines for a conventional diagnostic magnetic resonance (MR) system and a MR simulator (MR-SIM) system used for radiotherapy. METHODS: In this study, we compared QA testing guidelines from the American College of Radiology (ACR) MR Quality Control (MR QC) Manual to the QA section of the American Association of Physicists in Medicine (AAPM) Task Group 284 report (TG-284). Differences and similarities were identified in testing scope, frequency, and tolerances. QA testing results from an ACR accredited clinical diagnostic MR system following ACR MR QC instructions were then evaluated using TG-284 tolerances. RESULTS: Five tests from the ACR MR QC Manual were not included in TG-284. Five new tests were identified for MR-SIM systems in TG-284 and pertained exclusively to the external laser positioning system of MR-SIM systems. "Low-contrast object detectability" (LCD), "table motion smoothness and accuracy," "transmitter gain," and "geometric accuracy" tests differed between the two QA guides. Tighter tolerances were required in TG-284 for "table motion smoothness and accuracy" and "low contrast object detectability." "Transmitter gain" tolerance was dependent on initial baseline measurements, and TG-284 required that geometric accuracy be tested over a larger field of view than the ACR testing method. All tests from the ACR MR QC Manual for a conventional MR system passed ACR tolerances. The T2-weighted image acquired with ACR sequences failed the 40-spoke requirement from TG-284, transmitter gain was at the 5% tolerance of TG-284, and geometric accuracy could not be evaluated because of required equipment differences. Table motion passed both TG-284 and ACR required tolerances. CONCLUSION: Our study evaluated QA guidelines for an MR-SIM and demonstrated the additional QA requirements of a clinical diagnostic MR system to be used as an MR-SIM in radiotherapy as recommended by TG-284.

Understanding the Radiobiological Mechanisms Induced by 177Lu-DOTATATE in Comparison to External Beam Radiation Therapy.

Radionuclide Therapy (RNT) with 177Lu-DOTATATE targeting somatostatin receptors (SSTRs) in neuroendocrine tumours (NET) has been successfully used in routine clinical practice, mainly leading to stable disease. Radiobiology holds promise for RNT improvement but is often extrapolated from external beam radiation therapy (EBRT) studies despite differences in these two radiation-based treatment modalities. In a panel of six human cancer cell lines expressing SSTRs, common radiobiological endpoints (i.e., cell survival, cell cycle, cell death, oxidative stress and DNA damage) were evaluated over time in 177Lu-DOTATATE- and EBRT-treated cells, as well as the radiosensitizing potential of poly (ADP-ribose) polymerase inhibition (PARPi). Our study showed that common radiobiological mechanisms were induced by both 177Lu-DOTATATE and EBRT, but to a different extent and/or with variable kinetics, including in the DNA damage response. A higher radiosensitizing potential of PARPi was observed for EBRT compared to 177Lu-DOTATATE. Our data reinforce the need for dedicated RNT radiobiology studies, in order to derive its maximum therapeutic benefit.

Treatment of benign tumours and related pathologies with radiotherapy: experience of the General Hospital of Mexico.

Background: Benign diseases include tumours or localized growths with low potential for progression. The use of radiotherapy (RT) at a low dose (LD) or intermediate dose for benign pathologies has been widely proposed and studied. Currently, the use of RT is limited mainly to hyperproliferative and inflammatory diseases as a first or second line of treatment. Materials and methods: This was a retrospective, observational and descriptive study conducted in the Radiotherapy Unit of the Oncology Service of the General Hospital of Mexico "Dr. Eduardo Liceaga" from January 2, 2016, to December 31, 2020. Patients diagnosed with benign pathology and treated with RT were included. The response to treatment was recorded based on the imaging study report and/or clinical review that determined control of the disease, and toxicity was recorded based on the RTOG evaluation for acute effects and CTCAE V. 4.0 for chronic effects. Results: The records of 222 patients were analysed. The mean follow-up duration was 31.53 months (range 6-61), and the median was 24 months. Of all of the analysed pathologies that were treated with RT, keloid scars predominated in 112 patients (50.5%), and paragangliomas predominated in 72 patients (32.4%); the other patients were treated for rare pathologies. The prescribed dose was dependent on the diagnosis, with the mean dose being 31.63 Gy (1500-6000 cGy) and the median being 2000 cGy. Most of the cases of acute and chronic toxicity were grades 1 and 2, and a disease response was achieved in 94.1% of the patients. Conclusion: Our series shows that for cases of benign pathology, RT offers acceptable toxicity, improves quality of life and yields a good response, achieving disease control. These results suggest the inclusion of inflammatory pathology among the indications for treatment.

A comparative analysis between low-dose-rate brachytherapy and external beam radiation therapy for low- and intermediate-risk prostate cancer in Asian men.

OBJECTIVE: To report the long-term clinical outcomes of low-risk (LR) and intermediate-risk (IR) prostate cancer patients treated with low-dose-rate brachytherapy (LDR-BT) and external beam radiation therapy (EBRT). PATIENTS AND METHODS: Men with biopsy-proven low- and intermediate-risk prostate cancer received EBRT and LDR-BT in an Asian academic center from 2000 to 2019 were reviewed. Kaplan-Meier survival analysis was performed to compare biochemical failure-free survival (bFFS) and overall survival (OS) between LDR and EBRT in the low- and intermediate-risk cohorts. RESULTS: 642 patients (521 EBRT and 121 LDR-BT) with low- and intermediate-risk prostate cancer were included for analysis. In the intermediate-risk group, 5- and 10-year bFFS was 96%, 89% and 86%, 61% for LDR-BT and EBRT, respectively. LDR-BT was associated with a statistically significant improvement of bFFS in the intermediate-risk cohort (HR 2.7, p = 0.02). In the low-risk cohort, no difference of bFFS was found between LDR-BT and EBRT (HR 1.9, p = 0.08). Hormone therapy was more common in EBRT than LDR-BT for intermediate-risk group (71% versus 44%, p < 0.05). Prostate cancer-specific mortality was low in both EBRT (1%) and LDR-BT (2%) cohorts. No significant difference in OS was found between LDR-BT and EBRT in low- and intermediate-risk group (HR 2.1, p = 0.2 and HR = 1.7, p = 0.3). CONCLUSION: In our retrospective study, LDR-BT is associated with superior bFFS compared with EBRT in Asian men with intermediate-risk prostate cancer.

Role of Radiation Therapy for Newly Diagnosed Retroperitoneal Sarcoma.

OPINION STATEMENT: Soft tissue sarcomas (STS) are rare, aggressive, and heterogenous tumors, comprising approximately 1% of adult cancers with over 50 different subtypes. The mainstay of treatment for retroperitoneal sarcomas (RPS) includes surgical resection. The addition of radiation therapy (RT), either preoperatively or postoperatively, has been used to potentially decrease the risk of local recurrence. The recently published results from STRASS (EORTC-STBSG 62092-22092), which randomized patients to receive or not receive preoperative radiation, indicate no abdominal recurrence-free survival benefit (primary endpoint) nor overall survival benefit to date from the addition of preoperative RT prior to surgical resection in patients with RPS. Keeping in mind caveats of subgroup analyses, the data show a significant reduction in local recurrence with radiation therapy in resected patients and non-significant trends toward improved abdominal recurrence-free survival in all patients and improved local control and abdominal recurrence-free survival in patients with liposarcoma and low-grade sarcoma. Given the high rate of local failure with surgery alone, it is possible that higher RT dose and/or selective RT dose painting may improve outcomes. Prior to treatment, the authors encourage multidisciplinary review and discussion of management options at a sarcoma center for patients with RPS. Selective use of RT may be considered for patients at high risk of local recurrence.

Radical prostatectomy improves survival in selected metastatic prostate cancer patients: A North American population-based study.

OBJECTIVE: To test whether radical prostatectomy might result in better survival than external beam radiation therapy in metastatic prostate cancer patients. METHODS: Newly diagnosed metastatic prostate cancer patients with M1a/b substages, treated with radical prostatectomy or external beam radiation therapy were abstracted from the Surveillance, Epidemiology and End Results database (2004-2016). Temporal trend analyses, propensity score matching, cumulative incidence plots, multivariate competing risks regression models and landmark analyses were used. RESULTS: Of 4280 patients, 954 (22.3%) were treated with radical prostatectomy. After propensity score matching, 5-year cancer-specific mortality was 47.0 versus 53.0% in radical prostatectomy versus external beam radiation therapy patients (P = 0.003). In propensity score matched competing risks regression models, radical prostatectomy was associated with lower cancer-specific mortality versus external beam radiation therapy (hazard ratio 0.79, 95% confidence interval 0.79-0.90; P = 0.001). Finally, landmark analyses rejected the bias favoring radical prostatectomy. Finally, in subgroup analyses, we relied on selection criteria that most closely resembled the STAMPEDE criteria and a similar hazard ratio of 0.8 (P < 0.001) was recorded. CONCLUSION: In metastatic prostate cancer, radical prostatectomy results in lower cancer-specific mortality relative to external beam radiation therapy. Even after adjustment for age at diagnosis, prostate-specific antigen and biopsy Gleason grade grouping, lower cancer-specific mortality rates are recorded in radical prostatectomy patients than in external beam radiation therapy patients. As a result, radical prostatectomy should be considered as a treatment option in selected metastatic prostate cancer patients. However, further validation will be provided by ongoing clinical trials.

Long-term clinical outcomes of external beam radiation therapy for oligometastatic prostate cancer: A combination of prostate-targeted treatment and metastasis-directed therapy.

OBJECTIVE: To assess the efficacy of combination of prostate-targeted treatment and metastasis-directed therapy for oligometastatic prostate cancer. METHODS: We retrospectively evaluated the clinical outcomes of synchronously diagnosed oligometastatic prostate cancer patients treated with external beam radiation therapy for the prostate and all metastatic lesions (≤3 lesions) at Kyoto University Hospital between January 2004 and April 2019. The prescribed dose was basically ≥70 Gy for the prostate with or without whole pelvic irradiation, and ≥45 Gy for the metastatic lesions. Clinical outcomes were compared with a contemporary cohort of 55 synchronous oligometastatic prostate cancer patients treated with the standard of care. RESULTS: In total, 16 consecutive patients with synchronous oligometastatic prostate cancer were analyzed. The median follow-up period was 7.4 years. The 8-year overall survival, prostate cancer-specific survival, biochemical failure-free, clinical failure-free and castration-resistant prostate cancer-free rates were 64.8%, 71.3%, 38.5%, 47.3% and 67.3%, respectively. No grade 3 or higher radiation-induced late toxicities occurred. Patients with prostate-targeted treatment plus metastasis-directed therapy had a significantly higher castration-resistant prostate cancer-free rate than those without prostate-targeted treatment plus metastasis-directed therapy (P = 0.00741). CONCLUSIONS: Prostate-targeted treatment plus metastasis-directed therapy through external beam radiation therapy can result in favorable long-term disease-free and survival outcomes with acceptable morbidities among synchronous oligometastatic prostate cancer patients. Therefore, this approach may represent a promising treatment strategy for this population. Further investigation is required.

[How to improve radiotherapy ? Technological developments and radiotherapy of tomorrow]. / Comment améliorer la radiothérapie ? Évolutions technologiques et radiothérapie de demain.

Radiotherapy established itself in the 20th century as an essential modality in the fight against cancer. The major technological advances of the last decades have allowed a considerable improvement in the therapeutic window. They have also paved the way for stereotactic radiotherapy and new indications. The aim of this article is to enable readers to understand external radiotherapy in 2021 and to understand the challenges of tomorrow. Three areas of improvement in the discipline will be described, the optimization of the prescribed therapeutic dose, the improvement of the distribution of this dose and, finally, the better understanding of radiobiology. For each of these axes, the current implications will be described as well as those which could/should have a major impact on the radiotherapy. FLASH radiotherapy will also be discussed.

La radiothérapie s'est installée au 20ème siècle comme une modalité incontournable dans la lutte contre le cancer. Les avancées technologiques majeures des dernières décennies ont permis une amélioration considérable de la fenêtre thérapeutique. Elles ont également ouvert la voie à la radiothérapie stéréotaxique et à de nouvelles indications. Cet article a pour objectif de permettre aux lecteurs de comprendre la radiothérapie externe en 2021 et d'en appréhender les enjeux de demain. Trois axes d'amélioration de la discipline seront décrits, l'optimisation de la dose thérapeutique prescrite, l'amélioration de la distribution de cette dose et, finalement, la meilleure compréhension de la radiobiologie. Pour chacun de ces axes, des implications actuelles seront données ainsi que celles qui pourraient/ devraient avoir un impact sur la radiothérapie future. La radiothérapie FLASH sera, par exemple, abordée.

Potential alternative treatment approach for pediatric patient with diffusely infiltrative primary rhabdomyosarcoma of the liver.

Primary hepatic rhabdomyosarcoma is rare, making decisions regarding locoregional management with resection and/or conventional radiation difficult. We present a novel treatment approach for a pediatric patient diagnosed with rhabdomyosarcoma diffusely involving the liver. This patient underwent treatment with yttrium-90 (Y-90) microspheres followed by external beam radiation therapy (EBRT ) to residual disease, interdigitated with systemic chemotherapy. Initial post-radiation imaging showed significant response to treatment, and she experienced minimal acute toxicities and no long-term toxicities. She developed recurrent PET-avid disease 23 months after Y-90 treatment, necessitating further local and continued systemic therapies. We report on the tumor control following Y-90 and EBRT treatment.

Adjuvant radiotherapy in malignant tumors of parotid. Experience of the Navarra Hospital Complex.

BACKGROUND: The objective of the study was to review the outcome of patients with parotid cancer treated with postoperative radiotherapy at Complejo Hospitalario de Navarra in the last ten years. MATERIALS AND METHODS: We retrospectively reviewed patients treated with adjuvant radiotherapy between January 2008 and December 2018. We analyzed demographic data, histopathologic findings, local control (LC) and overall survival (OS). RESULTS: A total of 40 patients received postoperative radiotherapy during the period mentioned. There were 22 men (55%) and 18 women (45%). Median age was 58 years (19-90). By tumor histology, the most common was squamous cell carcinoma (22.5%) followed by ex-pleomorphic adenoma (15%) and adenoid cystic carcinoma (10%). According to Surgery, 19 patients (47.5%) underwent a total parotidectomy, 20 (50%) partial parotidectomy, and 1 (2.5%) a radical parotidectomy. Twenty-one patients (51.2%) underwent cervical dissection, most of them being supraomohyoid (31.7%). Reasons for adjuvant RT were: R1 resection (35% of the patients), high grade tumors (27.5%) and 17.5% because R1 surgery and R1. Radiation was administered using IMRT in most patients to a total dose of 60 Gy in 30 fractions. The 5-year overall survival (OS) (Kaplan-Meier) was 81% (95% CI: 68.5-96.2%), and 10-years - 64%. The 5-year local control (LC) (Kaplan-Meier) was 82.4% (95% CI: 91.46-73.33%) and the 10-year LC - 72.2% (95% CI: 54.9-96%). To date, only 4 patients (10%) have died due to their parotid tumor. CONCLUSION: The adjuvant radiotherapy added to surgery, significantly reduces the risk of recurrence in high-risk patients with a very acceptable survival rate.

Oncological outcomes for patients with locally advanced prostate cancer treated with neoadjuvant endocrine and external-beam radiation therapy followed by adjuvant continuous/intermittent endocrine therapy in an open-label, randomized, phase 3 trial.

BACKGROUND: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT). METHODS: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death. RESULTS: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722). CONCLUSIONS: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.

Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors.

BACKGROUND: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). METHODS: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18). RESULTS: The median follow-up time was 24 (range: 1-124) months. The median prescribed dose was 60 (6-70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0-87.6; SCRT: 50.4, 95% CI: 27.6-73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7-85.2; SCRT: 42.0, 95% CI: 17.7-70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2-86.4; SCRT: 42.0, 95% CI: 17.7-70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups. CONCLUSIONS: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

Can radiation-induced lower urinary tract disease be ameliorated in patients treated for pelvic organ cancer: ICI-RS 2019?

AIMS: This article reviews the clinical outcomes and basic science related to negative effects of radiotherapy (RT) on the lower urinary tract (LUT) when used to treat pelvic malignancies. METHODS: The topic was discussed at the 2019 meeting of the International Consultation on Incontinence-Research Society during a "think tank" session and is summarized in the present article. RESULTS: RT is associated with adverse effects on the LUT, which may occur during treatment or which can develop over decades posttreatment. Here, we summarize the incidence and extent of clinical symptoms associated with several modes of delivery of RT. RT impact on normal tissues including urethra, bladder, and ureters is discussed, and the underlying biology is examined. We discuss innovative in vivo methodologies to mimic RT in the laboratory and their potential use in the elucidation of mechanisms underlying radiation-associated pathophysiology. Finally, emerging questions that need to be addressed through further research are proposed. CONCLUSIONS: We conclude that RT-induced negative effects on the LUT represent a significant clinical problem. Although this has been reduced with improved methods of delivery to spare normal tissue, we need to (a) discover better approaches to protect normal tissue and (b) develop effective treatments to reverse radiation damage.