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Background The α/β ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. To do so, we carried out a randomized trial comparing hypofractionated and conventionally fractionated image-guided intensity modulated radiotherapy (IG-IMRT) in high-risk prostate cancer. Here, we report on acute toxicity and quality of life (QOL) for the first 124 randomized patients. Methods The trial compares 76 Gy in 38 fractions (5 fractions/week) (Arm 1) to 63 Gy in 20 fractions (4 fractions/week) (Arm 2) (IG-IMRT). Prophylactic pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially (Arm 1) and 44 Gy in 20 fractions simultaneously (Arm 2) was applied. All patients had long term androgen deprivation therapy (ADT) started before RT. Both physician-rated acute toxicity and patient-reported QOL using EPIC questionnaire are described. Results There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity. Compared to conventional fractionation (Arm 1), GI and GU toxicity both developed significantly earlier but also disappeared earlier in the Arm 2, reaching significant differences from Arm 1 at week 8 and 9. In multivariate analyses, only parameter shown to be related to increased acute Grade ≥1 GU toxicity was the study Arm 2 ( p  = 0.049). There were no statistically significant differences of mean EPIC scores in any domain and sub-scales. The clinically relevant decrease (CRD) in EPIC urinary domain was significantly higher in Arm 2 at month 1 with a faster recovery at month 3 as compared to Arm 1. Conclusions Hypofractionation at 3.15 Gy per fraction to 63 Gy within 5 weeks was well tolerated. The GI and GU physician-rated acute toxicity both developed earlier but recovered faster using hypofractionation. There was a correlation between acute toxicity and bowel and urinary QOL outcomes. Longer follow-up is needed to determine the significance of these associations with late toxicity.

Purpose To assess the overall clinical outcome of protocol-based image-guided salvage pulsed-dose-rate brachytherapy for locally recurrent prostate cancer after radiotherapy failure particularly regarding feasibility and side effects. Patients and methods Eighteen consecutive patients with locally recurrent prostate cancer (median age, 69 years) were treated during 2005–2011 with interstitial PDR brachytherapy (PDR-BT) as salvage brachytherapy after radiotherapy failure. The treatment schedule was PDR-BT two times with 30 Gy (pulse dose 0.6 Gy/h, 24 h per day) corresponding to a total dose of 60 Gy. Dose volume adaptation was performed with the aim of optimal coverage of the whole prostate (V 100 > 95 %) simultaneously respecting the protocol-based dose volume constraints for the urethra (D 0.1 cc < 130 %) and the rectum (D 2 cc < 50–60 %) taking into account the previous radiation therapy. Local relapse after radiotherapy (external beam irradiation, brachytherapy with J-125 seeds or combination) was confirmed mostly via choline-PET and increased PSA levels. The primary endpoint was treatment-related late toxicities—particularly proctitis, anal incontinence, cystitis, urinary incontinence, urinary frequency/urgency, and urinary retention according to the Common Toxicity Criteria. The secondary endpoint was PSA-recurrence-free survival. Results We registered urinary toxicities only. Grade 2 and grade 3 toxicities were observed in up to 11.1 % (2/18) and 16.7 % (3/18) of patients, respectively. The most frequent late-event grade 3 toxicity was urinary retention in 17 % (3/18) of patients. No late gastrointestinal side effects occurred. The biochemical PSA-recurrence-free survival probability at 3 years was 57.1 %. The overall survival at 3 years was 88.9 %; 22 % (4/18) of patients developed metastases. The median follow-up time for all patients after salvage BT was 21 months (range, 8–77 months). Conclusion Salvage PDR-brachytherapy of the prostate following local failure after radiation therapy is a treatment option with a low rate of genitourinary side effects and no late gastrointestinal side effects. The treatment efficacy in the first 3 years is promising.

Key Points More than half of all patients with cancer receive radiation therapy. Normal tissue tolerance for radiation limits the dose of radiation that can safely be delivered, which can limit the probability of curing a tumour. As our knowledge of the mechanisms and signalling pathways that determine the response of tumour tissues and normal tissues to radiation increases, targeted drugs can be developed that selectively sensitize tumours or protect normal tissues. Promising approaches to selectively enhance tumour radiosensitivity include triggering synthetic lethality, inhibiting multiple targets to simultaneously block more than one signalling pathway and targeting the tumour microenvironment. More than half of all patients with cancer receive radiation therapy, but normal tissue tolerance to radiation often limits the ability to cure tumours with radiation therapy. Here, Moding, Kastan and Kirsch discuss current approaches and possible future directions for combining radiation therapy with targeted therapies to enhance the probability of tumour cure. Approximately 50% of all patients with cancer receive radiation therapy at some point during the course of their treatment, and the majority of these patients are treated with curative intent. Despite recent advances in the planning of radiation treatment and the delivery of image-guided radiation therapy, acute toxicity and potential long-term side effects often limit the ability to deliver a sufficient dose of radiation to control tumours locally. In the past two decades, a better understanding of the hallmarks of cancer and the discovery of specific signalling pathways by which cells respond to radiation have provided new opportunities to design molecularly targeted therapies to increase the therapeutic window of radiation therapy. Here, we review efforts to develop approaches that could improve outcomes with radiation therapy by increasing the probability of tumour cure or by decreasing normal tissue toxicity.

Primary vaginal cancer is a rare cancer and clinical evidence to support recommendations on its optimal management is insufficient. Because primary vaginal cancer resembles cervical cancer in many aspects, treatment strategies are mainly adopted from evidence in locally advanced cervical cancer. To date, the organ-sparing treatment of choice is definitive radiotherapy, consisting of external beam radiotherapy and brachytherapy, combined with concurrent chemotherapy. Brachytherapy is an important component of the treatment and its steep dose gradient enables the delivery of high doses of radiation to the primary tumour, while simultaneously sparing the surrounding organs at risk. The introduction of volumetric CT or MRI image-guided adaptive brachytherapy in cervical cancer has led to better pelvic control and survival, with decreased morbidity, than brachytherapy based on x-ray radiographs. MRI-based image-guided adaptive brachytherapy with superior soft-tissue contrast has also been adopted sporadically for primary vaginal cancer. This therapy has had promising results and is considered to be the state-of-the-art treatment for primary vaginal cancer in standard practice.

To evaluate if topical support therapy during static-intensity modulated radiotherapy (sIMRT) course is able to equal the characteristic minimum risk for radiation proctitis of Image-guided volumetric modulated arc therapy (IG-VMAT) treatment among localized prostate cancer patients. Rectal toxicity data of the above patients were retrospectively collected throughout three different clinical periods at our Radiotherapy Deparment: from October 2011 to December 2012, prostate cancer patients were treated with sIMRT and in advance supported by means of daily topical corticosteroids; from January 2013 to November 2016, topical corticosteroids were replaced by daily hyaluronic acid enemas; from December 2016 to May 2018 eligible patients were treated with newly introduced IG-VMAT supported by only on-demand topical corticosteroids. Among 359 eligible patients, IG-VMAT was proven generally more effective than sIMRT supported by topical medications in terms of proctitis reduction, although without clinical and practical relevance. Topical medications might have a role in radiation proctitis prevention.

Background Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). Methods A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1–2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5–7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. Results The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. Conclusion The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction.

The goal of the study was to assess the impact of deep inspiration breath hold technique (DIBH), surface-guided radiotherapy (SGRT), and daily kilovoltage cone-beam computed tomography (kV-CBCT) on the dose to organs at risk (OAR) in left-sided breast cancer radiotherapy. Twenty-six consecutive left-sided breast cancer patients treated using Volumetric Intensity Modulated Arc Therapy (VMAT), DIBH, SGRT, and a hypofractionated regimen were retrospectively evaluated in this study. Dose parameters were extracted from dose-volume histograms (DVH). The Wilcoxon Matched Pairs test was used to test dose parameters obtained in free breathing (FB) and DIBH for statistical significance. Multivariable analysis of variance (ANOVA) and receiver operating characteristics (ROC) analysis were used to identify parameters and cut-off points associated with the reduction of the mean heart dose (MHD) by DIBH. Based on published models, the risk of cardiac and lung toxicity (pneumonitis) using SGRT or daily kV-CBCT was estimated and compared. DIBH substantially reduced the MHD (median, 43.6%; range, 4.2% to 75.1%; P < 0.00001). The risk of cardiac toxicity using SGRT increased by 1%, compared to 3.6% to 20.5% using daily kV-CBCT. No significant difference in the risk of radiation-induced pneumonitis using SGRT versus daily kV-CBCT was detected. The ANOVA revealed the relative increase of the left lung volume by DIBH as the only significant impact factor for the MHD. The ROC analysis of this parameter showed an area under the curve (AUC) of 0.89 (95%CI, 0.71 to 0.98; P < 0.0001). DIBH can substantially reduce the MHD in left-sided breast cancer patients treated with modern radiotherapy techniques and hypofractionation. Patient setup using SGRT compared to daily kV-CBCT may be the preferred option for many patients. In our patient cohort, the relative reduction of the left lung volume by DIBH can be used as a predictor to select patients who benefit from DIBH.

Objective: Cognitive decline and alopecia after radiotherapy are challenging problems. We aimed to compare whole brain radiotherapy (WBRT) plans reducing radiation dose to the hippocampus and scalp between helical tomotherapy (HT) and intensity-modulated proton therapy (IMPT). Methods: We conducted a planning study of WBRT for 10 patients. The clinical target volume was defined as the whole brain excluding the hippocampus avoidance (HA) region. The prescribed dose was 30 Gy in 10 fractions to cover 95% of the target. Constraint goals were defined for the target and organs at risk (OAR). Results: Both techniques met the dose constraints for the target and OAR. However, the coverage of the target (dose covering 95% [D95%] and 98% [D98%] of the volume) were better in IMPT than HT (HT vs IMPT: D95%, 29.9 Gy vs 30.0 Gy, P < .001; D98%, 26.7 Gy vs 28.1 Gy, P = .002). The homogeneity and conformity of the target were also better in IMPT than HT (HT vs IMPT: homogeneity index, 1.50 vs 1.28, P < .001; conformity index, 1.30 vs 1.14, P < .001). IMPT reduced the D100% of the hippocampus by 59% (HT vs IMPT: 9.3 Gy vs 3.8 Gy, P < .001) and reduced the Dmean of the hippocampus by 37% (HT vs IMPT: 11.1 Gy vs 7.0 Gy, P < .001) compared with HT. The scalp IMPT reduced the percentage of the volume receiving at least 20 Gy (V20Gy) and V10Gy compared with HT (HT vs IMPT: V20Gy, 56.7% vs 6.6%, P < .001; V10Gy, 90.5% vs 37.1%, P < .001). Conclusion: Both techniques provided acceptable target dose coverage. Especially, IMPT achieved excellent hippocampus- and scalp-sparing. HA-WBRT using IMPT is a promising treatment to prevent cognitive decline and alopecia.

The dosimetry of scalp dose was prospectively studied and correlated with alopecia following conventional cranial irradiation in primary brain tumors patients. Patients with primary brain tumors who required conventional radiotherapy were enrolled. A hairline marker was applied to the patient's scalp to identify the entire scalp region. The maximal dose to 2% volume of interest (D2) for the entire scalp region were obtained. The radiation dosages at the localized hair-loss areas were evaluated during the final week of RT (transient alopecia) and six months after completing RT (permanent alopecia). Kruskal-Wallis tests were used to compare the dosimetric parameter values with statistical significance set as p < 0.05. Forty-eight patients were included in the analysis. The prescribed radiation doses ranged from 50.4 to 60.0 Gy. Thirty-two patients experienced alopecia (27 transient and 5 permanent). The median D2 values adjusted for the entire scalp were higher in the alopecia group (38.40 Gy for transient alopecia and 47.84 Gy for permanent alopecia vs 11.90 Gy for no alopecia, p < 0.001). The D2 value was determined as a predictive parameter for alopecia. The threshold values for transient and permanent alopecia over the entire scalp were 22.15 Gy and 36.81 Gy, respectively. At the localized hair-loss areas, the D2 values for transient and permanent alopecia were higher at 44.82 Gy and 50.00 Gy, respectively. The radiation intensity at the localized hair-loss areas was also related to the severity of alopecia, with D2 values of 35.14 Gy and 46.39 Gy for clinically assigned grade 1 and grade 2 transient alopecia, respectively, with the D2 value being even higher for permanent alopecia. The D2 parameter value could be used to predict the type and severity of alopecia.

Background External beam radiation therapy (RT) has shown promising effects for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) in recent studies. However, there is still a lack of consensus on the optimal RT scheme for PVTT treatment. We evaluated the efficacy and safety of image-guided 10-fraction hypofractionated RT in these patients. Methods Between January 2016 and March 2022, a total of 95 HCC patients with PVTT received 10-fraction hypofractionated image-guided radiation therapy (IGRT) at two institutes, and 69 patients were analyzed. Follow-up imaging was performed at three-month intervals after the completion of RT. The extent of PVTT was described according to the Liver Cancer Study Group of Japan classification: Vp1 = segmental portal vein branch, Vp2 = right/left anterior/posterior portal vein, Vp3 = right/left portal vein, and Vp4 = main portal vein. Response evaluation was performed using Response Evaluation Criteria in Solid Tumors, version 1.1. Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) were calculated from the start date of RT. Results The median prescribed dose of 50 Gy (range: 40-50 Gy; biologically effective dose [BED]: 56-75Gy 10 ) was delivered in 10 fractions. In this cohort, 4.3% of patients had Vp1, 20.3% had Vp2, 37.7% had Vp3, and 37.7% had Vp4. Median Planning target volume was 105.3 cc (interquartile range [IQR], 74.1–179.4 cc). Fifty-two (75.4%) patients received 50 Gy. With a median follow-up of 10.2 months (IQR, 6–21 months), the median OS was 20.3 months, and 1-year FFLP, PFS, and OS rates were 88.7%, 26.9%, and 62.2%, respectively. At 3 months follow-up, 13.0% had a complete response, 36.2% had a partial response, 46.4% had a stable disease and 4.4% had a progressive disease. In the multivariate analysis, alpha-fetoprotein level ≥ 600 IU/ml (hazard ratio [HR] 2.06, p  = 0.03), Child–Pugh Class B or C (HR 2.30, p  = 0.02), and stage IVA or IVB (4.05, p  = 0.02) were significantly related to OS. During the follow-up period, there were 2 (2.9%) cases of grade ≥ 3 toxicity: grade 3 liver enzyme elevation ( n  = 1), and acute cholangitis ( n  = 1). Conclusions Hypofractionated RT demonstrated promising local PVTT control and OS rates with acceptable toxicity. These data suggest that 10-fraction image-guided hypofractionated RT (BED: 56–75 Gy 10 ) is a feasible treatment option for PVTT in HCC patients.