Late Rectal Toxicity Research Articles

Effect of Gross Tumor Volume (GTV) after Pelvic External Irradiation on Radiation Dose Selection and Prognosis in Vaginal Stump Cancer

<h3>Purpose/Objective(s)</h3> Radical radiotherapy is safe and effective for patients with vaginal stump cancer after hysterectomy. The tumor volume after external irradiation is important for selecting irradiation dose and local control. For patients with less residual tumor volume after external irradiation, the total irradiation dose < 70Gy does not affect survival. <h3>Materials/Methods</h3> Ninety-nine patients with vaginal stump cancer after hysterectomy between January 2011 and November 2018 were retrospectively analyzed in this study. All patients received radical radiotherapy without prior antitumor therapy. After pelvic irradiation of 45-50Gy, the residual tumor was further irradiated to 60-82Gy (EQD2, a/β=10) by external irradiation or brachytherapy. Cisplatin-based chemotherapy was performed concurrently with radiotherapy. The overall survival (OS), progress-free survival (PFS), local control (LC), and toxicity were analyzed. <h3>Results</h3> Seventy patients (70.7%) had received 70-82Gy (EQD2, a/β=10) for vaginal stump lesions, and external irradiation is responsible for 84.8% of patients. The Median follow-up was 49.9 months (7.4-114.7months). The 4-year actuarial OS, PFS, and LC were 84.4%, 79.2%, and 89.3%, respectively. In multivariable analysis, GTV > 9cc after pelvic radiotherapy an only independent prognostic factor for worse OS, LC (OS: hazard ratio [HR] = 6.87, CI, 1.90 to 24.83, p=0.003; LC: HR = 8.47, CI, 2.18 to 32.82, p = 0.002). In a subgroup analysis, among patients with GTV > 9cc after pelvic radiation, those with an irradiation dose ≥ 70Gy had better LC than those with a dose < 70Gy (86.5% VS. 44.4%, p=0.009). However, the OS or PFS did not show significant differences between the two groups. In patients with GTV ≤9cc, the irradiation dose ≥ 70Gy didn't show a benefit of LC (93.2% VS.100%, p=0.267). 6 patients (6.06%) developed acute grade 3 rectal toxicity, 4 of which occurred at irradiation dose ≥ 70Gy. None of the patients had complications of late G3-4 grade urinary, rectal toxicity, or lymphedema. <h3>Conclusion</h3> Radical radiotherapy is safe and effective for patients with vaginal stump cancer after hysterectomy. The tumor volume after external irradiation is important for selecting irradiation dose and local control. For patients with less residual tumor volume after external irradiation, the total irradiation dose < 70Gy does not affect survival.

Health-related quality of life of salvage prostate reirradiation using stereotactic ablative radiotherapy with urethral-sparing.

PurposeTo explore whether prostate motion mitigation using the rectal distension-mediated technique is safe and effective in stereotactic ablative radiation therapy (SABR) salvage treatment of intraprostatic cancer recurrences following initial radiotherapy for primary prostate cancer.Materials and methodsBetween July 2013 and December 2020, 30 patients received salvage SABR for 68Ga- PSMA-11 PET/CT-detected intra-prostatic relapses. Median time from primary RT to salvage reirradiation was 70.2 (IQR, 51.3-116.0) months. Median PSA at retreatment was 3.6 ng/mL (IQR, 1.9-6.2). Rectal distension-mediated SABR was achieved with a 150-cm3 air-inflated endorectal balloon and a Foley catheter loaded with 3 beacon transponders was used for urethra visualization and on-line tracking. MRI-based planning employed a 2-mm expansion around the planned target volume (PTV), reduced to 0-mm at the interface with critical organs at risk (OARs). Volumetric Modulated Arc Therapy (VMAT) permitted a 20% dose reduction of the urethra. VMAT simultaneous integrated boost (SIB) of the dominant intraprostatic lesion was deployed when indicated. Median SABR dose was 35 Gy (7 Gy per fraction over 5 consecutive days; range 35-40 Gy). Toxicity assessment used CTCAE v.4 criteria.ResultsMedian follow-up was 44 months (IQR, 18-60). The actuarial 3- and 4-year biochemical relapse free survival was 53.4% and 47.5%, respectively. Intraprostatic post-salvage relapse by PSMA PET/CT was 53.3%. Acute grade 2 and 3 genitourinary (GU) toxicities were 20% and 0%, respectively. There were no instances of acute grade ≥2 rectal (GI) toxicity. Late grade 2 and 3 GU toxicities occurred in 13.3% and 0% of patients, respectively. There were no instances of grade ≥2 late rectal toxicity. Patient-reported QOL measures showed an acute transient deterioration in the urinary domain 1 month after treatment but returned to baseline values at 3 months. The median IPSS scores rose over baseline (≥5 points in 53% of patients) between month 6 and 12 post-treatment as a result of urinary symptoms flare, eventually receding at 18 months. The bowel domain metrics had no appreciable changes over time.ConclusionPursuit of local control in intraprostatic failures is feasible and can be achieved with an acceptably low toxicity profile associated with effective OAR sparing.

A comparison between high dose rate brachytherapy and stereotactic body radiotherapy boost after elective pelvic irradiation for high and very high-risk prostate cancer.

PurposeTo compare biochemical recurrence-free survival (BRFS) and toxicity outcomes of high dose rate brachytherapy (HDRB) and stereotactic body radiotherapy (SBRT) boost after elective nodal irradiation for high/very high-risk prostate cancer.Materials and MethodsA retrospective analysis was performed in 149 male patients. In 98 patients, the boost to the prostate was delivered by HDRB as 2 fractions of 10 Gy (EQD2 for α/β = 1.5; 66 Gy) or 1 fraction of 15 Gy (EQD2 for α/β = 1.5; 71 Gy). In 51 male patients, SBRT was used for the boost delivery (3 fractions of 7 Gy; EQD2 for α/β = 1.5; 51 Gy) because brachytherapy equipment was out of order. ResultsIn 98 patients that received HDRB boost, 3- and 5-year BRFS were 74.6% and 66.8%. Late grade-II genitourinary toxicity was detected in 27, grade-III in 1 case. Grade-II (maximum) rectal toxicity was diagnosed in nine patients. For 51 male patients that received SBRT boost, 3- and 5-year BRFS was 76.5% and 67.7%. Late grade-II (maximum) genitourinary toxicity was detected in five cases, late grade-II rectal toxicity in four cases. Other three patients developed late grade-III–IV rectal toxicity that required diverting colostomy. SBRT boost was associated with higher maximum dose to 2 cm3 of anterior rectal wall (D2cm³rectum) compared to HDRB: 92% versus 55% of dose to prostate. Severe rectal toxicity was negligible at EQD2 D2cm³rectum <85 Gy and EQD2 D5cm³ rectum <75 Gy.ConclusionOur results indicate similar 3- and 5-year BRFS in patients with high/very high-risk prostate cancer who received HDRB or SBRT boost, but SBRT boost is associated with higher rate of severe late rectal toxicity.

A prospective comparative study of concurrent chemoradiation in advanced carcinoma cervix patients with weekly cisplatin vs. weekly cisplatin and paclitaxel

Background: Cisplatin-based concurrent chemoradiation is the standard treatment for carcinoma cervix. However, there is a need to explore alternative chemotherapeutic agents to further improve the treatment outcome. In this study, weekly paclitaxel and cisplatin-based chemoradiation was compared with weekly cisplatin-based chemoradiation in terms of disease control and toxicity profile. Materials and Methods: Sixty-four patients with FIGO stage IB2-IIIB squamous cell carcinoma of the uterine cervix were divided (by simple random sampling) into two groups: control arm patients who received radiotherapy (50 Gy in 25 fractions over 5 weeks) with concurrent weekly cisplatin (40 mg/m2) and study arm patients received same radiation dose with weekly cisplatin (30 mg/m2) and paclitaxel (40 mg/m2). After that, all patients received brachytherapy 21 Gy/three fractions, one fraction/week. All patients were followed up weekly during treatment, then 4–6 weeks after treatment completion, and thereafter monthly for at least 6 months. Results: The overall treatment response (complete+ partial response) was numerically higher in the cisplatin-containing control arm, but not significant (93% vs. 80%, P-value = 0.406). High-grade early rectal (60% vs. 25%, P-value = 0.014) and acute gastrointestinal toxicity (66% vs. 6%, P-value &lt;0.001) were significantly higher in the cisplatin and paclitaxel-containing arm. Hematological, renal, late rectal, and bladder toxicities were also numerically higher in the study arm, but not statistically significant. Conclusion: There was no significant benefit of weekly paclitaxel and cisplatin as an alternative to weekly cisplatin-based chemoradiation in the treatment of carcinoma cervix.

Brachytherapy focal dose escalation using ultrasound based tissue characterization by patients with non-metastatic prostate cancer: Five-year results from single-center phase 2 trial

This prospective trial investigates side effects and efficacy of focal dose escalation with brachytherapy for patients with prostate cancer. In the Phase II, monocentric prospective trial 101 patients with low-/intermediate- and high-risk prostate cancer were enrolled between 2011 and 2013. Patients received either PDR-/HDR-brachytherapy alone with 86-90 Gy (EQD2, α/β = 3 Gy) or PDR-/HDR-brachytherapy as boost after external beam radiation therapy up to a total dose of 91-96 Gy (EQD2, α/β = 3 Gy). Taking place brachytherapy all patients received the simultaneous integrated focal boost to the intra-prostatic tumor lesions visible in computer-aided ultrasonography (HistoScanning™) - up to a total dose of 108-119 Gy (EQD2, α/β = 3 Gy). The primary endpoint was toxicity. Secondary endpoints were cumulative freedom from local recurrence, PSA-free survival, distant metastases-free survival, and overall survival. This trial is registered with ClinicalTrials.gov, number NCT01409876. Median follow-up was 65 months. Late toxicity was generally low with only four patients scoring urinary grade 3 toxicity (4/101, 4%). Occurrence of any grade of late rectal toxicities was very low. We did not register any grade ≥2 of late rectal toxicities. The cumulative 5 years local recurrence rate (LRR) for all patients was 1%. Five years- biochemical disease-free survival estimates according Kaplan-Meier were 98,1% and 81,3% for low-/intermediate-risk and high-risk patients, respectively. Five years metastases-free survival estimates according Kaplan-Meier were 98,0% and 83,3% for all patients, low-/intermediate-risk and high-risk patients, respectively. The 5 years-results from this Phase II Trial show that focal dose escalation with computer-aided ultrasonography and brachytherapy for patients with non-metastatic prostate cancer is safe and effective.

Dosimetric feasibility of moderately hypofractionated/dose escalated radiation therapy for localised prostate cancer with intensity-modulated proton beam therapy using simultaneous integrated boost (SIB-IMPT) and impact of hydrogel prostate-rectum spacer

PurposeTo examine the dosimetric feasibility of hypofractionated/dose escalated radiation therapy in patients with localized prostate carcinoma using simultaneous integrated boost intensity-modulated proton beam therapy (SIB-IMPT) in absence or presence of prostate-rectum spacer.MethodsIMPT technique was implemented in 23 patients with intermediate- and high-risk prostate cancer treated at West German Proton Therapy Centre from March 2016 till June 2018, using SIB technique prescribing 60 GyRBE and 72 GyRBE in 30 fractions to PTV1 (prostate and seminal vesicle) and PTV2 boost (prostate and proximal seminal vesicle), respectively. In 15 patients, a transperineal injection of hydrogel was applied prior to radiotherapy to increase the distance between prostate and rectum. Planning and all treatments were performed with a 120 ml fluid-filled endorectal balloon customised daily for each patient. For each patient, 2 lateral IMPT beams were implemented taking a field-specific range uncertainty (RU) into account. Dose volume histograms (DVH) were analyzed for PTV2, PTV2 with range uncertainty margin (PTV2RU), rectum, bladder, right/left femoral heads, and penile bulb. For late rectal toxicities, the normal tissue complication probabilities (NTCP) were calculated using different biological models. A DVH- and NTCP-based dosimetric comparison was carried out between non-spacer and spacer groups.ResultsFor the 23 patients, high-quality plans could be achieved for target volume and for other organs at risk (OARs). For PTV2, the V107% was 0% and the Dmax did not exceed 106.2% of the prescribed dose. The volume PTV2RU covered by 95% of the dose ranged from 96.16 to 99.95%. The conformality index for PTV2RU was 1.12 ± 0.057 and the homogeneity index (HI) was 1.04 ± 0.014. Rectum Dmax and rectal volume receiving 73–50 Gy could be further reduced for the spacer-group. Significant reductions in mean and median rectal NTCPs (stenosis/necrosis, late rectal bleeding ≥ 2, and late rectal toxicities ≥ 3) were predicted for the spacer group in comparison to the non-spacer group.ConclusionHypofractionated/dose escalated radiotherapy with SIB-IMPT is dosimetrically feasible. Further reduction of the rectal volumes receiving high and medium dose levels (73–50 Gy) and rectal NTCP could be achieved through injection of spacers between rectum and prostate.

MRI-Based Radiotherapy Planning to Reduce Rectal Dose in Excess of Tolerance.

Materials and Methods This prospective single-arm study enrolled 15 men treated with IG-IMRT for localized prostate cancer. All participants received a dedicated 3 Tesla MRI examination of the prostate in addition to a pelvic CT examination for treatment planning. Two volumetric modulated arc therapy (VMAT) plans with a prescription dose of 79.2 Gy were designed using identical constraints based on CT- and MRI-defined consensus volumes. The volume of rectum exposed to 70 Gy or more was compared using the Wilcoxon paired signed rank test. Results For CT-based treatment plans, the median volume of rectum receiving 70 Gy or more was 9.3 cubic centimeters (cc) (IQR 7.0 to 10.2) compared with 4.9 cc (IQR 4.1 to 7.8) for MRI-based plans. This resulted in a median volume reduction of 2.1 cc (IQR 0.5 to 5.3, P < .001). Conclusions Using MRI to plan prostate IG-IMRT to a dose of 79.2 Gy reduces the volume of rectum receiving radiation dose in excess of tolerance (70 Gy or more) and should be considered in men who are at high risk for late rectal toxicity and are not good candidates for other rectal sparing techniques such as hydrogel spacer. This trial is registered with NCT02470910.

Lower Bladder Toxicity of SalvageVersusAdjuvant Modern Radiotherapy for Prostate Cancer Patients

In prostate cancer, postoperative radiotherapy timing is debated to avoid overtreatments and toxicities. This study compared acute and late rectal and bladder toxicities in the adjuvant and salvage setting. In total, 129 patients were analyzed in two groups: adjuvant radiotherapy (aRT) and salvage radiotherapy (sRT). In aRT and sRT, grade 1 (G1) acute bladder toxicities were detected in 40 and 30 patients, and grade 2 (G2) in 1 and 6; G1 late bladder toxicities were described in 30 and 20, and G2 in 6 and 2, respectively. In aRT and sRT, acute G1 rectal toxicities were reported in 18 and 27 patients, and G2 in 5 and 4, respectively. Late rectal G1 toxicities were observed in 10 patients, G2 in 6 and G3 in 1 in the aRT. In sRT, 8 patients and 1 developed G1 and G2 toxicities, respectively. Regarding bladder toxicity, a higher incidence occurred in aRT; late toxicity was lower in sRT. Adjuvant and salvage RT in prostate cancer treatment resulted in acceptable toxicities.

Clinical outcomes of patients treated with template-based high-dose-rate interstitial brachytherapy boost for post-operative recurrent gynecological malignancies: A retrospective analysis.

To report the clinical outcomes in patients treated with Martinez universal perineal interstitial template (MUPIT)-based interstitial brachytherapy boost for primary and recurrent vault and vaginal cancers, and to perform a comparative analysis with our previously published series of similar patients. One hundred and seventeen patients treated between January, 2009 and December, 2015 were evaluated. Descriptive statistics for the patterns of relapse, local recurrence-free survival (LRFS), disease-free survival (DFS), overall survival (OS), and late toxicities were carried out. Kaplan-Meier curves were used for survival analysis. All variables with the potential to affect outcomes were tested using log-rank test for statistical significance. At a median follow-up of 63 months, LRFS, DFS, and OS at 3/5 years were 77.1%/74.7%, 61%/52%, and 72.3%/63.1%, respectively. Overall treatment time (OTT) of 56 days did not affect outcomes. Bulky tumors and OTT > 63 days adversely affected LRFS. Overall treatment time also significantly impacted DFS and OS. Grade 3-4 late bladder toxicities were observed in 1.7% patients, and grade 3-4 late rectal toxicities in 5% patients. Compared to our previous series, the outcome in the current series is better in terms of severe late toxicities (5% improvement in rectal toxicity, and 2.7% improvement in bladder toxicity) and OS by 10%. This could be attributed to the increasing use of concurrent chemotherapy and relative optimization strategies for organs at risk. Patients with primary and recurrent vault and vaginal cancers treated with high-dose-rate interstitial brachytherapy boost using MUPIT resulted in modest clinical outcomes and acceptable late toxicities. OTT was the most important factor affecting the outcomes.

Acute and Late Rectal Toxicity Following Hypofractionated Radiotherapy in Patients With Prostate Cancer: Results of a Prospective Study.

Previous randomized clinical trials have shown that moderate hypofractionation has a non-inferior or even superior efficacy to conventionally fractionated external beam radiation therapy (EBRT) in low and intermediate-risk prostate cancer. We herein aimed to evaluate the acute and late gastrointestinal (GI) toxicity of hypofractionated radiotherapy (HRT) in a real-world setting. Patients with intermediate-risk prostate adenocarcinoma eligible to receive HRT were prospectively enrolled. All patients were submitted to rectoscopy after completion of HRT, every three months after radiotherapy for the first year and every six months for the second year. Toxicity events were classified as acute, when presenting during radiotherapy or within the first three months following its completion, and as late when appearing three months to three years post-HRT. Twenty prostate cancer patients participated in this study and received 22 sessions of HRT (5 sessions a week; 2.75 Gy per session) and an overall dose of 60.5 Gy. None of our patients developed acute GI toxicity; late GI toxicity (RTOG/EORTC grade 3 rectal bleeding) was observed in 1 patient only (1/20, 5%), at 6- and 12-months post-HRT. No rectal mucosa damage was observed on follow-up rectoscopy in the acute phase in any of our patients; five patients (5/20, 25%) developed late telangiectasias. Vienna retroscopy score (VRS) was 1 in 4/5 patients (80%) and 2 in 1/5 (20%). Minimal radiation-induced rectal mucosal damage was observed in our patient population, and only as a late event, further attesting to the safety of HRT in this setting.

Salvage Treatments for the Local Recurrence of Prostate Cancer After Radiotherapy – Results of an International Multidisciplinary Survey

The treatment of local recurrences of prostate cancer after radical radiation therapy (RT) varies widely. The aim of this study was to evaluate the international practice patterns and opinions from a multidisciplinary point of view.A web-based survey was spread between 26 May 2020 and 28 February 2021 through social media and personal contacts, aiming to reach all countries where RT for prostate cancer is delivered. We sought to obtain a balanced feedback from radiation oncologists and urologists (the primary physicians who manage local recurrences after RT) from each country, as well as clinical and medical oncologists. A proportional representation of countries according to the number of RT centers was intended. The survey had a decision tree design, with a total of 45 questions.We received 1030 responders from 114 countries. There were 51.1% radiation oncologists, 37.2% urologists, 5.2% clinical oncologists and 5.3 % medical oncologists. Most respondents work in academic centers (56.3%), have more than 20 years' experience in treating prostate cancer (56.4%) and at least 10 prostate cancer patients under active treatment/month (53.4%). Almost 17% of the respondents declared not using any salvage treatment in case of a local recurrence after RT. The main reasons of not recommending salvage prostatectomy were: concerns on safety (68%), efficacy (33.7%), local protocols (22.7%), or availability (22.7%). For those who chose to avoid re-irradiation, the reasons were concerns on safety (70.7%), efficacy (43.1%), local protocols (26.9%) or availability (10.8%). In case of cryotherapy and HI-FU, the main issue was availability (71.9%), followed by concerns on efficacy (41.5%), safety (25.7%), local protocols (20.5%) or reimbursement (12.3%). Those not recommending salvage treatments, reported as "usually" preferred option GnRH agonist (64%), antiandrogens (49%), active surveillance, (32%) chemotherapy (27%), or observation (24%). The most important factors considered as contraindication for salvage therapies mentioned by participants consider this for local recurrence after RT of prostate cancer were: life expectancy < 5 years (71.5%), no biopsy or imaging confirmation (61.1%), rectal late toxicity after first treatment (46.8%), coexisting relapse in the regional lymph nodes (33.8%). The following salvage treatments were used "Often", "Usually" or "Always": radical prostatectomy (48.9%), HDR-BT (37%), SBRT (36.6%), IMRT (25.4%), LDR-BT (18.4%), HI-FU (15.4%), proton therapy (12.5%). When making the treatment decision, 73.4% of the participants declared that they "Always" or "Usually" present the case in a tumor board.Salvage treatments for recurrent prostate cancer after radical RT are frequently recommended. However, there are significant concerns on efficacy, safety and availability. Radical prostatectomy remains the preferred option, but re-irradiation is often used as an alternative.

Influence of hydrogel spacer placement with prostate brachytherapy on rectal and urinary toxicity.

To determine the influence of rectal hydrogel spacer placement (HSP) on late rectal toxicity outcomes in prostate cancer patients treated with low-dose-rate (LDR) brachytherapy, with or without supplemental external beam radiotherapy (EBRT). A total of 224 patients underwent LDR brachytherapy with HSP, as monotherapy or combined with EBRT, between January 2016 and December 2019. Dosimetric variables reflecting the extent of rectal sparing and late rectal toxicity outcomes were evaluated. This spacer cohort was retrospectively compared to a similar patient group (n = 139) in whom HSP was not used. Hydrogel spacer placement was associated with significantly reduced rectal doses for all dosimetric variables; the median percentage rectal dose to 1 cc of rectum and rectal dose to 2 cc of rectum of the spacer cohort were all significantly lower compared to the non-spacer cohort. The incidence rates of overall (any grade) and grade ≥2 rectal toxicity were lower in patients with HSP compared to patients who did not undergo HSP: 12% and 1.8% vs 31% and 5.8%, respectively. The 3-year cumulative incidence of overall rectal toxicity was significantly lower with HSP than without (15% vs 33%; P < 0.001), corresponding to an overall rectal toxicity reduction on univariable analysis (hazard ratio 0.45, 95% confidence interval 0.28-0.73; P = 0.001). In this patient cohort treated with prostate brachytherapy, none of the urethral dosimetric variables or the presence or absence of HSP was associated with late urinary toxicity. Hydrogel rectal spacer placement is a safe procedure, associated with significantly reduced rectal dose. HSP translates to a decrease in overall late rectal toxicity in patients receiving dose-escalated brachytherapy-based procedures.

PP08 Presentation Time: 11:10 AM: Influence of Hydrogel Spacer Placement in Conjunction with Prostate Brachytherapy with or without External Beam Radiotherapy on Rectal Toxicity Outcomes

Purpose: This study aimed to determine the influence of hydrogel rectal spacer placement (HSP) on late rectal toxicity outcomes in prostate cancer patients treated with low dose rate (LDR) brachytherapy with or without supplemental external beam radiotherapy (EBRT).

Incidence and dosimetric predictive factors of late rectal toxicity after low-dose-rate brachytherapy combined with volumetric modulated arc therapy in high-risk prostate cancer at a single institution: Retrospective study

PurposeThe purpose of this study is to investigate the incidence of rectal toxicity and to identify the associated dosimetric predictive parameters after I-125 seed low-dose-rate brachytherapy (LDR-BT) combined with volumetric modulated arc therapy (VMAT) and dose constraints. Methods and MaterialsIn total, 110 patients with high-risk prostate cancer received 110 Gy LDR-BT, followed by 45 Gy VMAT. Rectal toxicity was recorded according to Common Terminology Criteria for Adverse Events v.4.03. The dosimetric factors associated with LDR-BT and VMAT were analyzed to determine their relationship with rectal toxicity. Receiver operating characteristic (ROC) curve analysis was performed for ≥ grade 2 (G2) rectal toxicity prediction. ResultsThe follow-up duration was 10.1–115.2 months (median 60.5 months). Seven patients had G2 rectal hemorrhage, and none of the patients had grade 3 rectal hemorrhage. In the univariate analysis, the rectal volume receiving 100% of the prescribed dose (rV100) (p < 0.001), the dose covering 2 cc of the rectum (rD2cc) during LDR-BT (p = 0.002), and the combined rD2cc during LDR-BT and VMAT (p = 0.001) were identified as predictors of G2 rectal hemorrhage. In the ROC curve analysis, the cutoff value was 0.46 cc for rV100, 74.0 Gy for rD2cc, and 86.8 GyEQD2 for combined rD2cc. ConclusionPredictors of late ≥ G2 rectal hemorrhage are rV100, rD2cc, and combined rD2cc. The incidence of rectal toxicity is low and acceptable in this setting and is highly dependent on the rectal dose of LDR-BT. The use of higher-quality LDR-BT and VMAT dose constraints may further reduce the rate of rectal hemorrhage.

Focal Brachytherapy for Localized Prostate Cancer: Midterm Outcomes

PurposeFocal brachytherapy (F-BT) is a suitable technique for focal therapy in localized prostate cancer. It has the ability to adapt the seed implantation to the volume and location of the tumor. The aim of this study was to assess F-BT oncologic, functional, and toxicity midterm outcomes in men who underwent prostate cancer treatment. Methods and MaterialsThe study included 39 men with low- to intermediate-risk prostate cancer treated with F-BT between 2010 and 2015. The dose prescription was 145 Gy. Failure was defined as the presence of any residual prostate cancer in the treated area. The primary and secondary endpoints were the F-BT oncologic and functional outcomes, respectively. A 2-sided P value < .05 indicated statistical significance. ResultsThe mean follow-up time was 65 months (range, 43-104 months). After 24 months, 34 patients underwent control biopsies and 5 patients refused. The biopsies were negative in 27 cases (79%) and positive in 7 cases (21%), all outside the volume treated. Biochemical relapse-free survival at 5 years, disease-free survival, and overall survival were 96.8% ± 0.032%, 79.5% ± 0.076%, and 100%, respectively. The mean International Prostate Symptom Score at 2 months was significantly higher than initially (P = .0003), with no significant difference later. No late urinary, sexual, or rectal toxicity was observed. Salvage treatment was possible with good tolerance at 3.4 years of follow-up. Limitations of this study include the retrospective nature and lack of randomization. ConclusionsF-BT is a safe and effective treatment for selected patients presenting with low- or intermediate-risk localized prostate cancer.

Estimates of Alpha/Beta (α/β) Ratios for Individual Late Rectal Toxicity Endpoints: An Analysis of the CHHiP Trial

PurposeChanges in fraction size of external beam radiation therapy exert nonlinear effects on subsequent toxicity. Commonly described by the linear-quadratic model, fraction size sensitivity of normal tissues is expressed by the α/β ratio. We sought to study individual α/β ratios for different late rectal effects after prostate external beam radiation therapy.Methods and MaterialsThe CHHiP trial (ISRCTN97182923) randomized men with nonmetastatic prostate cancer 1:1:1 to 74 Gy/37 fractions (Fr), 60 Gy/20 Fr, or 57 Gy/19 Fr. Patients in the study had full dosimetric data and zero baseline toxicity. Toxicity scales were amalgamated to 6 bowel endpoints: bleeding, diarrhea, pain, proctitis, sphincter control, and stricture. Lyman-Kutcher-Burman models with or without equivalent dose in 2 Gy/Fr correction were log-likelihood fitted by endpoint, estimating α/β ratios. The α/β ratio estimate sensitivity was assessed using sequential inclusion of dose modifying factors (DMFs): age, diabetes, hypertension, inflammatory bowel or diverticular disease (IBD/diverticular), and hemorrhoids. 95% confidence intervals (CIs) were bootstrapped. Likelihood ratio testing of 632 estimator log-likelihoods compared the models.ResultsLate rectal α/β ratio estimates (without DMF) ranged from bleeding (G1 + α/β = 1.6 Gy; 95% CI, 0.9-2.5 Gy) to sphincter control (G1 + α/β = 3.1 Gy; 95% CI, 1.4-9.1 Gy). Bowel pain modelled poorly (α/β, 3.6 Gy; 95% CI, 0.0-840 Gy). Inclusion of IBD/diverticular disease as a DMF significantly improved fits for stool frequency G2+ (P = .00041) and proctitis G1+ (P = .00046). However, the α/β ratios were similar in these no-DMF versus DMF models for both stool frequency G2+ (α/β 2.7 Gy vs 2.5 Gy) and proctitis G1+ (α/β 2.7 Gy vs 2.6 Gy). Frequency-weighted averaging of endpoint α/β ratios produced: G1 + α/β ratio = 2.4 Gy; G2 + α/β ratio = 2.3 Gy.ConclusionsWe estimated α/β ratios for several common late adverse effects of rectal radiation therapy. When comparing dose-fractionation schedules, we suggest using late a rectal α/β ratio ≤ 3 Gy.

Curative 3D Conformal Radiotherapy of Non-Operated Prostate Adenocarcinoma at Pointe-a-Pitre University Hospital (Guadeloupe): About 29 Cases

Context: Technological advances have improved the toxicities of radiotherapy. We are evaluating the 3D technique in prostate cancer. Materials and Methods: Retrospective study from January 2015 to December 2015 with 29 files. Survival was calculated by Kaplan-Meier method. Results: We collected 29 patient records over the study period. The median age was 75 years with the following extremes: 54 years and 83 years. The median PSA level was 12 ng/ml with a range of 3.05 to 79 ng/ml. Gleason score analysis showed 6 patients (20.69%) with a score of 6 (3 + 3), 23 patients (79.31%) with a score of 7 including 12 patients (41.38%) with grade 3 and 11 patients (37.93%) with grade 4. The median dose delivered was 74 Gy, with a mean dose of 73.79 Gy and extremes of 70 Gy for the minimum and 76 Gy for the maximum. Hormone therapy was combined with radiotherapy in 17 patients (58.62%). Seven patients (24.14%) had grade 1 acute bladder toxicity and one patient (3.45%) had grade 2 acute toxicity. Late bladder toxicity was grade 1 in 5 patients (17.24%), grade 2 in 3 patients (10.34%) and grade 3 in 1 patient (3.45%). Late rectal toxicity, grade 2 in 3 patients (10.34%), grade 3 in 1 patient, was noted. Overall survival at 2 years was 100% and 89.65% at 5 years. Relapse-free survival at 2 years was 82.76% and 62.07% at 5 years. There were 3 deaths (10.34%) of which only one was related to prostate cancer. Conclusion: Radiotherapy, like surgery, is a fundamental option for the treatment of prostate cancers, particularly those that are locally advanced. It is gaining in importance with the improvement of techniques (IMRT, VMAT…) and new fractionations which contribute to the reduction of toxicities and the comfort of patients (shorter spread).

Temporal course of late rectal toxicity & impact of intervention in patients undergoing radiation for cervical cancer.

Background & objectives:There is limited information available on the temporal course of late stage radiotherapy adverse effects. The present study reports on the temporal course of late toxicities after chemoradiation and brachytherapy.Methods:Women with cervical cancer who presented with late toxicity after (chemo) radiation were included in the study. Grade of toxicity (Clinical Toxicity Criteria for Adverse Events version 4.03) and type of intervention were recorded at three-monthly interval for the first year and then six monthly until 24 months. Direct cost for the management of toxicity was calculated. Univariate analysis was performed to understand the impact of various factors on persistence of toxicity.Results:Ninety two patients were included in this study. Grades I, II, III and IV toxicities were observed in 50 (54%), 33 (36%), 7 (8%) and 2 (2%) patients, respectively, at first reporting. Patients spent a median of 12 (3-27) months with toxicity. At 12 months, 48/92 (52.2%) patients had a complete resolution of toxicity, whereas 27/92 (29.3%) patients had low grade (I-II) persistent toxicity. Only 6/92 (6.5%) patients who had grade III−IV toxicity had resolution to a lower grade. Four (4.3%) patients died due to toxicity. At 24 months, 9 (10%) patients continued to have grade ≥ III toxicity. On an average, 7 (2-24) interventions were required for the clinical management of late toxicity and median direct cost incurred was ₹ 50,625 (1,125-303,750).Interpretation & conclusions:In this study late radiation toxicity resolved within 12 months in more than half of patients. However, others are likely to have had persistent lower grade toxicity or progression to higher grade. Structured strategies are hence needed for the effective management of late toxicities.

Prospective evaluation of probabilistic dose-escalated IMRT in prostate cancer.

BackgroundCure- and toxicity rates after intensity-modulated radiotherapy (IMRT) of prostate cancer are dose-and volume dependent. We prospectively studied the potential for organ at risk (OAR) sparing and compensation of tumor movement with the coverage probability (CovP) concept.Patients and methodsTwenty-eight prostate cancer patients (median age 70) with localized disease (cT1c–2c, N0, M0) and intermediate risk features (prostate-specific antigen [PSA] < 20, Gleason score ≤ 7b) were treated in a prospective study with the CovP concept. Planning-CTs were performed on three subsequent days to capture form changes and movement of prostate and OARs. The clinical target volume (CTV) prostate and the OARs (bladder and rectum) were contoured in each CT. The union of CTV1–3 was encompassed by an isotropic margin of 7 mm to define the internal target volume (ITV). Dose prescription/escalation depended on coverage of all CTVs within the ITV. IMRT was given in 39 fractions to 78 Gy using the Monte-Carlo algorithm. Short-term androgen deprivation was recommended and given in 78.6% of patients.ResultsLong-term toxicity was evaluated in 26/28 patients after a median follow-up of 7.1 years. At last follow-up, late bladder toxicity (Radiation Therapy Oncology Group, RTOG) G1 was observed in 14.3% of patients and late rectal toxicities (RTOG) of G1 (7.1%) and of G2 (3.6%) were observed. No higher graded toxicity occurred. After 7.1 years, biochemical control (biochemically no evidence of disease, bNED) was 95.5%, prostate cancer-specific survival and the distant metastasis-free survival after 7.1 years were 100% each.ConclusionsCovP-based IMRT was feasible in a clinical study. Dose escalation with the CovP concept was associated by a low rate of toxicity and a high efficacy regarding local and distant control.

Efficacy and Toxicity of Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Twelve-Year Study

This is the first study using Stereotactic Body Radiotherapy (SBRT) for organ confined prostate cancer to have patients with twelve-year follow-up. In this study, we report outcomes for prostate robotic SBRT in 560 patients, with NCCN low-, intermediate- and high- risk disease. We report on biochemical disease-free survival (bDFS), toxicity and Quality of Life (QOL). We studied 560 patients with organ-confined prostate cancer, treated with SBRT to a dose covering the PTV (prostate +3-5 mm) of 35-36.25 Gy. The prostate was covered by a dose of 38.4-40 Gy. Treatment was delivered in 5 daily fractions between 2006-2009. We included 45 high risk patients who received a 18-21 Gy SBRT boost after 45 Gy to the pelvis with EBRT. Median follow up is 132 months. The median age was 69 years, and median PSA was 6.58. 324 patients were low-risk, 153 were intermediate-risk and 83 were high-risk. ADT up to 9 months was administered to 102 patients. Patients were further stratified into low-intermediate risk versus high-intermediate risk, with high-intermediate risk criteria of Gleason 4+3 = 7 or >1 intermediate risk factors (cT2b-c, PSA 10-20, Gleason 7). Biochemical failure was assessed using the Phoenix criterion. Cox regression analysis was used to determine which risk factors were significantly associated with increased risk of biochemical failure. Twelve-year bDFS was 92.0, 79.1 and 64.0% for low, intermediate and high-risk group patients, respectively. Local control was 97.0, 91.7 and 88.0% respectively. Favorable intermediate-risk patients had excellent outcomes, with no significant difference compared to low-risk patients with 12-year bDFS 89.8 vs 92.0%, respectively (p = 0.35). Unfavorable intermediate-risk patients had outcomes similar to high risk patients, with 12-year bDFS of 67.5 and 64.0% respectively (p = .24). Median PSA declined to 0.1. For low and intermediate risk patients, Gleason score was the only significant factor predicting for biochemical failure on multivariate analysis (p = 0.0003), with ADT, dose and PSA not significant. For high risk patients, PSA was the only significant predictor of bDFS (p = .01), with Gleason score, ADT or EBRT not significant. Toxicity was mild. 36.25 Gy was associated with more Grade 2-3 late urinary toxicity than 35 Gy. (13.8% vs 6%) p = .01 Patients receiving EBRT had a higher rate of late Grade 2 late rectal toxicity. Mean EPIC QOL urinary and bowel domains for all patients declined during the first 3 months and then returned to baseline, where they remain. Mean sexual QOL scores have slowly declined by 47% This study suggests that early excellent control rates for SBRT for prostate cancer remain durable over 12 years. Similarly, toxicity rates remain low and QOL scores remain high over that period. For patients receiving SBRT alone, 35 Gy is as effective as 36.25 Gy with less urinary toxicity, suggesting 35 Gy may be the optimal dose. For high risk patients, use of EBRT and ADT do not appear to increase long term control rates.