Hypofractionated radiotherapy after conservative surgery may increase low-intermediate grade late fibrosis in breast cancer patients.

AIM: To compare late toxicity after postoperative hypofractionated radiotherapy (RT) and standard fractionated RT in patients with early-stage breast carcinoma. METHODS: This retrospective study included 447 patients (Modulated Accelerated Radiotherapy [MARA-1]: 317 patients, and control group [CG]: 130 patients). In the CG, the whole breast received 50.4 Gy in 28 fractions (fx) using 3D-radiotherapy, plus a sequential electron boost (10 Gy in 4 fx) to tumor bed. In MARA-1 group, a forward-planned intensity-modulated radiotherapy technique with 40 Gy in 16 fx with a concomitant boost of 4 Gy to breast was used. The primary endpoint was to evaluate late toxicity, and secondary endpoints were acute toxicity, local control, and survival. ClinicalTrials.gov: NCT03461224. RESULTS: Median follow-up was 52 months (range: 3-115 months). Late skin and subcutaneous toxicity were acceptable: 5-year actuarial cumulative incidence of Grade (G) 3 late skin toxicity was 1.5% in CG and 0.0% in MARA-1. Five-year actuarial cumulative incidence of G3 late subcutaneous toxicity was 0.8% in CG and 0.3% in MARA-1. On multivariate analysis, tobacco smoking and planning target volume were associated with an increased risk of late G1 skin toxicity (HR: 2.15, 95% CI: 1.38-3.34 and HR: 1.12, 95% CI: 1.07-1.18, respectively), whereas patients with a larger planning target volume also showed an increased risk of G1 and G2 late subcutaneous toxicity (HR: 1.14, CI 95%: 1.08-1.20 and HR: 1.14, 95% CI: 1.01-1.28, respectively). MARA-1 patients also showed an increased risk of late G1 and G2 subcutaneous toxicity (HR: 2.35, 95% CI: 1.61-3.41 and HR: 3.07, 95% CI: 1.11-8.53, respectively) compared to CG. CONCLUSION: In this retrospective analysis, postoperative accelerated-hypofractionated RT for early-stage-breast carcinoma was associated with higher incidence of subcutaneous side effects. However, this increase was limited to G1-G2 toxicity. In the future, development of predictive models could help in tailoring dose and fractionation based on the risk of toxicity.

Optimal beam margins in linac-based VMAT stereotactic ablative body radiotherapy: a Pareto front analysis for liver metastases.

We explored the Pareto fronts mathematical strategy to determine the optimal block margin and prescription isodose for stereotactic body radiotherapy (SBRT) treatments of liver metastases using the volumetric-modulated arc therapy (VMAT) technique. Three targets (planning target volumes [PTVs] = 20, 55, and 101 cc) were selected. A single fraction dose of 26 Gy was prescribed (prescription dose [PD]). VMAT plans were generated for 3 different beam energies. Pareto fronts based on (1) different multileaf collimator (MLC) block margin around PTV and (2) different prescription isodose lines (IDL) were produced. For each block margin, the greatest IDL fulfilling the criteria (95% of PTV reached 100%) was considered as providing the optimal clinical plan for PTV coverage. Liver Dmean, V7Gy, and V12Gy were used against the PTV coverage to generate the fronts. Gradient indexes (GI and mGI), homogeneity index (HI), and healthy liver irradiation in terms of Dmean, V7Gy, and V12Gy were calculated to compare different plans. In addition, each target was also optimized with a full-inverse planning engine to obtain a direct comparison with anatomy-based treatment planning system (TPS) results. About 900 plans were calculated to generate the fronts. GI and mGI show a U-shaped behavior as a function of beam margin with minimal values obtained with a +1 mm MLC margin. For these plans, the IDL ranges from 74% to 86%. GI and mGI show also a V-shaped behavior with respect to HI index, with minimum values at 1 mm for all metrics, independent of tumor dimensions and beam energy. Full-inversed optimized plans reported worse results with respect to Pareto plans. In conclusion, Pareto fronts provide a rigorous strategy to choose clinical optimal plans in SBRT treatments. We show that a 1-mm MLC block margin provides the best results with regard to healthy liver tissue irradiation and steepness of dose fallout.

Dietary anthocyanins and health: data from FLORA and ATHENA EU projects.

Adherence to a 'Mediterranean diet' has been shown to be beneficial to human health. Fruit and vegetables represent some of the main components of the Mediterranean diet and their role has been increasingly considered in the process of preventing or reducing the risk of chronic degenerative diseases, such as cerebrovascular or coronary heart disorders, cancer and neurodegenerative diseases. To investigate the beneficial effect of these dietary compounds, two EU-funded projects were conducted during the last 10 years. Their results from experimental models suggest that dietary anthocyanin enrichment is beneficial against a number of ischemic and degenerative conditions. On the other hand, human studies demonstrated that anthocyanin supplementation can counteract the inflammatory response to stress conditions, such as a fatty meal. Moreover, an intervention trial in patients with breast cancer undergoing radiotherapy is presently testing the possible beneficial effect of the administration of a product enriched in anthocyanins on the inflammatory response to radiation and on its consequent skin toxicity, as well as on systemic low-grade inflammation reaction.

Linac-based extracranial radiosurgery with Elekta volumetric modulated arc therapy and an anatomy-based treatment planning system: Feasibility and initial experience.

We reported our initial experience in using Elekta volumetric modulated arc therapy (VMAT) and an anatomy-based treatment planning system (TPS) for single high-dose radiosurgery (SRS-VMAT) of liver metastases. This study included a cohort of 12 patients treated with a 26-Gy single fraction. Single-arc VMAT plans were generated with Ergo++ TPS. The prescription isodose surface (IDS) was selected to fulfill the 2 following criteria: 95% of planning target volume (PTV) reached 100% of the prescription dose and 99% of PTV reached a minimum of 90% of prescription dose. A 1-mm multileaf collimator (MLC) block margin was added around the PTV. For a comparison of dose distributions with literature data, several conformity indexes (conformity index [CI], conformation number [CN], and gradient index [GI]) were calculated. Treatment efficiency and pretreatment dosimetric verification were assessed. Early clinical data were also reported. Our results reported that target and organ-at-risk objectives were met for all patients. Mean and maximum doses to PTVs were on average 112.9% and 121.5% of prescribed dose, respectively. A very high degree of dose conformity was obtained, with CI, CN, and GI average values equal to 1.29, 0.80, and 3.63, respectively. The beam-on-time was on average 9.3 minutes, i.e., 0.36min/Gy. The mean number of monitor units was 3162, i.e., 121.6MU/Gy. Pretreatment verification (3%-3mm) showed an optimal agreement with calculated values; mean γ value was 0.27 and 98.2% of measured points resulted with γ < 1. With a median follow-up of 16 months complete response was observed in 12/14 (86%) lesions; partial response was observed in 2/14 (14%) lesions. No radiation-induced liver disease (RILD) was observed in any patients as well no duodenal ulceration or esophagitis or gastric hemorrhage. In conclusion, this analysis demonstrated the feasibility and the appropriateness of high-dose single-fraction SRS-VMAT in liver metastases performed with Elekta VMAT and Ergo++ TPS. Preliminary clinical outcomes showed a high rate of local control and minimum incidence of acute toxicity.

Volumetric modulated arc therapy (VMAT) and simultaneous integrated boost in head-and-neck cancer: is there a place for critical swallowing structures dose sparing?

OBJECTIVE: To explore the potential of volumetric-modulated arc therapy (VMAT) to reduce the risk of swallowing problems after curative chemoradiotherapy. METHODS: 20 patients with head and neck cancer who previously underwent radiotherapy were selected. Radiotherapy was prescribed according to simultaneous integrated boost technique with all targets irradiated simultaneously over 30 daily fractions. Doses of 70.5 (67.5), 60.0 and 55.5 Gy were prescribed to primary tumour, high-risk nodal regions and low-risk nodal regions, respectively. Pharyngeal constrictor muscles (PCM) and glottic and supraglottic larynx (SGL) were considered organs at risk related to swallowing dysfunction (SW-OARs). Upper pharyngeal constrictor muscles (uPCM), middle pharyngeal constrictor muscles (mPCM) and lower pharyngeal constrictor muscles (lPCM) part of PCM were also outlined separately. Clinical standard plans (standard-VMAT) and plans aiming to spare SW-OARs (swallowing dysfunction-VMAT) were also created. Normal tissue complication probabilities (NTCP) for physician-rated swallowing dysfunction were calculated using a recently predictive model developed by Christianen et al. RESULTS: Planning with two strategies demonstrated comparable planning target volume coverage and no differences in sparing of parotid glands and other non-swallowing organs at risk. SW-VMAT plans provided mean dose reduction for uPCM and SGL by 3.9 and 4.5 Gy, respectively. NTCP values for Radiation Therapy Oncology Group grade 2-4 swallowing dysfunction was decreased by 9.2%. Dose reductions with SW-VMAT depended on tumour location and overlap with SW-OARs. CONCLUSION: VMAT plans aiming at sparing swallowing structures are feasible, providing a significant reduction in NTCP swallowing dysfunction with respect to conventional VMAT. ADVANCES IN KNOWLEDGE: Dysphagia is today considered one of the dose-limiting toxicities of chemoradiotherapy. The dose sparing of swallowing structures represents a major challenge in radiotherapy. VMAT is a complex new technology having the potential to significantly reduce the risk of dysphagia after curative chemoradiotherapy.

Initial clinical experience with Epid-based in-vivo dosimetry for VMAT treatments of head-and-neck tumors.

We evaluated an EPID-based in-vivo dosimetry algorithm (IVD) for complex VMAT treatments in clinical routine. 19 consecutive patients with head-and-neck tumors and treated with Elekta VMAT technique using Simultaneous Integrated Boost strategy were enrolled. In-vivo tests were evaluated by means of (i) ratio R between daily in-vivo isocenter dose and planned dose and (ii) γ-analysis between EPID integral portal images in terms of percentage of points with γ-value smaller than one (γ%) and mean γ-values (γmean), using a global 3%-3 mm criteria. Alert criteria of ±5% for R ratio, γ% < 90% and γmean > 0.67 were chosen. A total of 350 transit EPID images were acquired during the treatment fractions. The overall mean R ratio was equal to 1.002 ± 0.019 (1 SD), with 95.9% of tests within ±5%. The 2D portal images of γ-analysis showed an overall γmean of 0.42 ± 0.16 with 93.3% of tests within alert criteria, and a mean γ% equal to 92.9 ± 5.1% with 85.9% of tests within alert criteria. Relevant discrepancies were observed in three patients: a set-up error was detected for one patient and two patients showed major anatomical variations (weight loss/tumor shrinkage) in the second half of treatment. The results are supplied in quasi real-time, with IVD tests displayed after only 1 minute from the end of arc delivery. This procedure was able to detect when delivery was inconsistent with the original plans, allowing physics and medical staff to promptly act in case of major deviations between measured and planned dose.

On the cutting edge of intensity modulated radiotherapy and simultaneous integrated boost (IMRT-SIB): The case of a patient with 8 brain metastases.

BACKGROUND: Patients with multiple brain metastases, especially those with more than 3 lesions, usually undergo to palliative whole brain (WB) radiotherapy (RT). METHODS: A breast cancer patient with 8 brain metastases was treated on the brain by a radical RT regimen. Prescription doses were according to the simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) technique with all lesions as well brain irradiated simultaneously in 20 daily fractions. Doses of 40.0 Gy (2.0 Gy/fraction) and 50.0 Gy (2.5 Gy/fraction) were prescribed to the whole brain and to eight individual metastases, respectively. RESULTS: Mean volume of the eight metastases was 8.1 cc (range: 3.8-10.1 cc). For all lesions, the volume receiving 95% of prescribed dose was 100% and dose homogeneity was within 3%. Moreover, maximum doses were less than 105% of prescribed dose, while average mean dose to lesions was 50.6 Gy (range: 49.7-51.5 Gy). Whole brain mean dose was 45.2 Gy. Maximum doses to brainstem and optic chiasma were limited to 44.5 Gy and 42.9 Gy, respectively, while maximum doses to eyes, lens and optic nerves were limited to 9.2 Gy, 4.9 Gy and 41.0 Gy, respectively. From a clinical point of view, subsequent MRI brain controls showed a complete clinical response. Forty months after treatment the patient is disease free and shows no late brain and skin toxicities. CONCLUSION: This case demonstrates the technical feasibility of a SIB-IMRT treatment in patients with more than 3 brain metastases.

Radioprotective effect of calcium channel blockers against late rectal bleeding in prostate cancer.

OBJECTIVE: This study was done to assess the impact of clinical factors and in particular the use of drugs for concomitant illnesses on late radiation-induced rectal bleeding in patients with prostate cancer. MATERIALS AND METHODS: Patients with histologically proven prostate adenocarcinoma treated with radical radiotherapy and followed up for at least 6 months were selected. The correlation between late rectal bleeding and a number of factors was investigated by univariate and multivariate analysis. RESULTS: A total of 278 patients who underwent radiotherapy at our institution between October 2002 and May 2011 were selected. At univariate analysis, delivery of radiation doses higher than 70 Gy and use of angiotensin-converting enzyme inhibitors were associated with a higher incidence of rectal bleeding. Conversely, patients who used calcium channel blockers had a lower risk (3-year rectal bleeding-free survival 89.8 versus 66.5 %, p = 0.043). At multivariate analysis, use of calcium channel blockers was found to have a protective effect with a hazard ratio of 0.3 (95 % CI 0.12-0.96). Delivery of higher radiation doses was associated with an increased risk of rectal bleeding (hazard ratio 3.02, 95 % CI 1.23-7.38). CONCLUSIONS: Use of calcium channel blockers during and after radiotherapy treatment might have a protective effect against late rectal bleeding. If these results are reconfirmed by larger clinical series, calcium channel blockers may be tested as radioprotector agents in clinical trials.

Assessing the feasibility of volumetric-modulated arc therapy using simultaneous integrated boost (SIB-VMAT): An analysis for complex head-neck, high-risk prostate and rectal cancer cases.

Intensity-modulated radiotherapy (IMRT) allowed the simultaneous delivery of different doses to different target volumes within a single fraction, an approach called simultaneous integrated boost (SIB). As consequence, the fraction dose to the boost volume can be increased while keeping low doses to the elective volumes, and the number of fractions and overall treatment time will be reduced, translating into better radiobiological effectiveness. In recent years, volumetric-modulated arc therapy (VMAT) has been shown to provide similar plan quality with respect to fixed-field IMRT but with large reduction in treatment time and monitor units (MUs) number. However, the feasibility of VMAT when used with SIB strategy has few investigations to date. We explored the potential of VMAT in a SIB strategy for complex cancer sites. A total of 15 patients were selected, including 5 head-and-neck, 5 high-risk prostate, and 5 rectal cancer cases. Both a double-arc VMAT and a 7-field IMRT plan were generated for each case using Oncentra MasterPlan treatment planning system for an Elekta Precise linac. Dosimetric indexes for targets and organs at risk (OARs) were compared based on dose-volume histograms. Conformity index, homogeneity index, and dose-contrast index were used for target analyses. The equivalent uniform doses and the normal tissue complication probabilities were calculated for main OARs. MUs number and treatment time were analyzed to score treatment efficiency. Pretreatment dosimetry was performed using 2-dimensional (2D)-array dosimeter. SIB-VMAT plans showed a high level of fluence modulation needed for SIB treatments, high conformal dose distribution, similar target coverage, and a tendency to improve OARs sparing compared with the benchmark SIB-IMRT plans. The median treatment times reduced from 13 to 20 minutes to approximately 5 minutes for all cases with SIB-VMAT, with a MUs reduction up to 22.5%. The 2D-array ion-chambers' measurements reported an agreement of more than 95% for a criterion of 3% to 3mm. SIB-VMAT was able to combine the advantages of conventional SIB-IMRT with its highly conformal dose distribution and OARs sparing and the advantages of 3D-conformal radiotherapy with its fast delivery.

Forward-planned intensity modulated radiation therapy using a cobalt source: A dosimetric study in breast cancer.

This analysis evaluates the feasibility and dosimetric results of a simplified intensity-modulated radiotherapy (IMRT) treatment using a cobalt-therapy unit for post-operative breast cancer. Fourteen patients were included. Three plans per patient were produced by a cobalt-60 source: A standard plan with two wedged tangential beams, a standard tangential plan optimized without the use of wedges and a plan based on the forward-planned "field-in-field" IMRT technique (Co-FinF) where the dose on each of the two tangential beams was split into two different segments and the two segments weight was determined with an iterative process. For comparison purposes, a 6-MV photon standard wedged tangential treatment plan was generated. Dmean, D98%, D2%, V95%, V107%, homogeneity, and conformity indices were chosen as parameters for comparison. Co-FinF technique improved the planning target volume dose homogeneity compared to other cobalt-based techniques and reduced maximum doses (D2%) and high-dose volume (V110%). Moreover, it showed a better lung and heart dose sparing with respect to the standard approach. The higher dose homogeneity may encourage the adoption of accelerated-hypofractionated treatments also with the cobalt sources. This approach can promote the spread of breast conservative treatment in developing countries.

Extracranial radiosurgery with volumetric modulated arc therapy: Feasibility evaluation of a phase I trial.

The aim of this study was to report early clinical experience in stereotactic body radiosurgery (SBRS) delivered using volumetric intensity modulated arc therapy (VMAT) in patients with primary or metastatic tumors in various extra-cranial body sites. Each enrolled subject was included in a different phase I study arm, depending on the tumor site and the disease stage (lung, liver, bone, metastatic), and sequentially assigned to a particular dose level. Technical feasibility and dosimetric results were investigated. The acute toxicity, tumor response and early local control were also studied. In total, 25 lesions in 20 consecutive patients (male/female, 11/9; median age, 67 years; age range, 47-86 years) were treated. Of these 25 lesions, 4 were primary or metastatic lung tumors, 6 were liver metastases, 8 were bone metastases and 7 were nodal metastases. The dose-volume constraints for organs at risk (OARs) were observed in 19 patients using a single-arc technique. Only in one patient were two arcs required. The treatment was performed without interruption or any other technical issues. The prescribed dose ranged from 12-26 Gy to the planning target volume (PTV). Delivery time ranged from 4 min to 9 min and 13 sec (median, 6 min and 6 sec). No incidence of grade 2-4 acute toxicity was recorded. The overall response rate was 48% (95% confidence interval (CI), 24.2-70.2) based on computed tomography (CT)/magnetic resonance imaging (MRI) and 89% (95% CI, 58.6-98.7) based on the positron emission tomography (PET) scan. SBRS delivered by means of VMAT allowed the required target coverage to be achieved while remaining within the normal tissue dose-volume constraints in the 20 consecutive patients. VMAT-SBRS resulted in adequate technical feasibility; the maximum tolerable dose has not yet been reached in any study arm.

Hypofractionated intensity-modulated radiotherapy with simultaneous integrated boost after radical prostatectomy: preliminary results of a phase II trial.

AIM: To report the acute toxicity of a hypofractionated regimen of intensity-modulated radiotherapy with simultaneous integrated boost (SIB-IMRT) to the pelvic nodes and the prostatic bed after radical prostatectomy. PATIENTS AND METHODS: Patients with prostate adenocarcinoma at high risk of relapse after radical prostatectomy or with biochemical relapse were deemed eligible for study. SIB-IMRT was prescribed to the whole pelvis (45-Gy delivered in 1.8-Gy fractions) and the prostatic bed [62.5 Gy, 2.5-Gy fractions, Equivalent Dose in 2-Gy fraction (EQD2)=68.75 Gy, α/ß=3]. Acute toxicity was recorded and graded according to Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Forty-nine patients were enrolled. No cases of grade ≥ 3 acute toxicity were recorded. Grade 2 acute genitourinary and gastrointestinal toxicity was observed in 9.6% and 29.7% of patients, respectively. CONCLUSION: After radical prostatectomy, hypofractionated high-dose SIB-IMRT enables for reduction of the overall treatment time, with an acute toxicity profile which compares favourably with that of conventionally fractionated high-dose three-dimensional conformal radiotherapy (3D-CRT).

Applicator-guided volumetric-modulated arc therapy for low-risk endometrial cancer.

The aim of this study was to report the feasibility of volumetric-modulated arc therapy (VMAT) in the postoperative irradiation of the vaginal vault. Moreover, the VMAT technique was compared with 3D conformal radiotherapy (3D-CRT) and fixed-field intensity-modulated radiotherapy (IMRT), in terms of target coverage and organs at risk sparing. The number of monitor units and the delivery time were analyzed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a 2D array of ionization chambers. Twelve patients with endometrial carcinoma who underwent radical hystero-adenexectomy and fixed-field IMRT treatments were retrospectively included in this analysis; for each patient, plans were compared in terms of dose-volume histograms, homogeneity index, and conformity indexes. All techniques met the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformity at all dose levels. VMAT resulted in significant reduction of rectal and bladder volumes irradiated at all dose levels compared with 3D-CRT. No significant differences were found with respect to IMRT. Moreover, a significant improvement of the dose conformity was reached by VMAT technique not only at the 95% dose level (0.74 vs. 0.67 and 0.62) but also at 50% and 75% levels of dose prescription. In addition, VMAT plans showed a significant reduction of monitor units by nearly 28% with respect to IMRT, and reduced treatment time from 11 to <3 minutes for a single 6-Gy fraction. In conclusion, VMAT plans can be planned and carried out with high quality and efficiency for the irradiation of vaginal vault alone, providing similar or better sparing of organs at risk to fixed-field IMRT and resulting in the most efficient treatment option. VMAT is currently our standard approach for radiotherapy of low-risk endometrial cancer.

Postoperative intensity-modulated radiotherapy with simultaneous integrated boost in prostate cancer: a dose-escalation trial.

OBJECTIVES: To determine the recommended phase II dose of postoperative accelerated intensity modulated radiotherapy (IMRT) for prostate cancer. MATERIAL AND METHODS: Step and shoot IMRT with simultaneous integrated boost (SIB) was delivered in 25 fractions over 5 weeks to patients with high risk resected prostate adenocarcinoma (stage pT3-4 and/or positive surgical margins). Pelvic nodes received 45 Gy at 1.8 Gy/fraction; dose escalation was performed only to the prostate bed (planned dose escalation: 56.8 Gy at 2.27 Gy/fraction, 59.7 Gy at 2.39 Gy/fraction, 61.25 Gy at 2.45 Gy/fraction, 62.5 Gy at 2.5 Gy/fraction). Dose-limiting toxicity (DLT) was any grade ≥ 3 acute toxicity (RTOG score). RESULTS: Twenty-five patients were treated: 7 patients at the 56.75 Gy dose level, 6 patients at each subsequent dose level. Pathologic stages were: pT2c: 2; pT3a: 11; pT3b: 12; pN0: 22; pN1: 3; R0: 7; R1: 18. Median follow-up time was 19 months (range: 6-36 months). No patient experienced DLT. Grade 1-2 acute rectal and urologic toxicity was common (17 and 22 patients, respectively). CONCLUSIONS: The recommended dose was 62.5 Gy in 2.5 Gy/fraction. Postoperative hypofractionated IMRT SIB for prostate cancer seemed to be well tolerated and could be tested in phase II studies.

Penile Metastases of Recurrent Prostatic Adenocarcinoma without PSA Level Increase: A Case Report.

We report a case of penile metastases from recurrent prostatic adenocarcinoma that was the first sign of a widespread metastatic disease in the absence of any increase in prostate-specific antigen (PSA) level. In April 2011, an 80-year-old man presented to our Radiotherapy Unit with multiple palpable hard nodules in the penis, dysuria, and moderate perineal pain, 7 years after he had received radiotherapy for prostate cancer. Nodules in the penis had appeared in February 2011. The ultrasound and magnetic resonance (MR) imaging suggested the diagnosis of multiple penile metastases. A total body computed tomography scan revealed a systemic spread of the disease, with multiple metastases in the liver, bones, and lungs. PSA level was 0.126 ng/ml. A fine needle aspiration biopsy of the liver lesion was undertaken, and the histopathologic examination revealed the prostatic origin of the metastases, so androgen deprivation therapy was started. The diagnosis of metastases should be considered in a patient with prior history of prostate malignancies presenting with solid nodules in the penis, even if the PSA level is low.

Early radiation-induced mucosal changes evaluated by proctoscopy: predictive role of dosimetric parameters.

BACKGROUND AND PURPOSE: Late rectal complications are assessed according to different scoring systems. Endoscopy can provide a more sensitive estimation of early radiation damage. The aim of this paper is to investigate the correlation between dosimetric parameters and rectal mucosal changes after radiotherapy (RT). MATERIALS AND METHODS: Patients with prostate adenocarcinoma treated with curative or adjuvant RT underwent endoscopy 1 year after RT. Receiver operating characteristics (ROC) analysis was performed to analyze the predictive capability of the dosimetric variables in determining mucosal changes classified by Vienna Rectoscopy Score (VRS). RESULTS: The best dosimetric predictors of grade ≥2 telangiectasia were rectal (r) V(60 Gy) (p=0.014), rV(70 Gy) (p=0.017) and rD(mean) (p=0.018). Similar results were obtained for grade ≥2 VRS. The set of rV(60 Gy)<34.4%, rV(70 Gy)<16.7% and rD(mean)<57.5 Gy was associated with a decreased risk of grade ≥2 telangiectasia and VRS. CONCLUSIONS: rV(60 Gy), rV(70 Gy) and rD(mean) were the strongest predictors of rectal mucosal alterations. In-depth analysis is required to correlate each mucosal alteration with late rectal toxicity in order to suggest early proctoscopy as surrogate end-point for rectal late toxicity in studies aimed at reducing this important complication.

Early proctoscopy is a surrogate endpoint of late rectal toxicity in prostate cancer treated with radiotherapy.

PURPOSE: To predict the grade and incidence of late clinical rectal toxicity through short-term (1 year) mucosal alterations. METHODS AND MATERIALS: Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy underwent proctoscopy a year after the course of radiotherapy. Mucosal changes were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were analyzed according to the Kaplan-Meier method. Comparison between prognosis groups was performed by log-rank analysis. RESULTS: After a median follow-up time of 45 months (range, 18-99), the 3-year incidence of grade ≥ 2 rectal late toxicity according to the criteria of the European Organization for Research and Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade ≥ 2 clinical rectal late toxicity was higher in patients with grade ≥ 2 (32% vs. 15 %, p = 0.02) or grade ≥ 3 VRS telangiectasia (47% vs. 17%, p ≤ 0.01) and an overall VRS score of ≥ 2 (31% vs. 16 %, p = 0.04) or ≥ 3 (48% vs. 17%, p = 0.01) at the 1-year proctoscopy. CONCLUSIONS: Early proctoscopy (1 year) predicts late rectal bleeding and therefore can be used as a surrogate endpoint for late rectal toxicity in studies aimed at reducing this frequent complication.

Intensity-modulated radiotherapy with simultaneous integrated boost to dominant intraprostatic lesion: preliminary report on toxicity.

OBJECTIVES: To evaluate the feasibility of intensity-modulated radiotherapy with simultaneous integrated boost to the dominant intraprostatic lesion for definitive treatment of prostate cancer. MATERIALS AND METHODS: Patients were deemed eligible for the study if they had histologically proven stage cT2-T3 N0M0 prostate adenocarcinoma. In addition <20% risk of lymph nodal involvement according to Roach formula, was required for enrollment. Patients were treated with intensity-modulated radiotherapy with simultaneous integrated boost technique to the dominant intraprostatic lesion defined by magnetic resonance imaging. The prescribed dose to the prostate and seminal vesicles was 72 Gy (1.8 Gy per fraction). The dose delivered to the intraprostatic lesion received was 80 Gy (2 Gy per fraction). Acute gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated weekly during treatment, and at 1 and 3 months thereafter. Late GI and GU toxicity was evaluated by Kaplan Meier method. RESULTS: Forty patients were deemed evaluable. Acute and late GI and GU toxicity were evaluated in all patients. Two patients (5%) developed acute grade 3 GI toxicity and 1 patient (2.5%) developed acute grade 3 GU toxicity. No grade 4 acute GI or GU toxicity occurred. With a median follow-up of 19 months (interquartile range, 15 to 26 mo), the 2-year actuarial cumulative incidence of grade ≥2 rectal toxicity was 9.5%. The 2-year actuarial cumulative incidence of grade ≥2 urinary toxicity was 13.3%. CONCLUSIONS: Treatment related acute toxicity was low in our cohort. Prolonged observation with a larger series of patients is necessary to evaluate late toxicity and local control.

Forward planned intensity modulated radiotherapy (IMRT) for whole breast postoperative radiotherapy. Is it useful? When?

The purpose was to compare the dosimetric results observed in 201 breast cancer patients submitted to tangential forward intensity-modulated radiation therapy (IMRT) with those observed in 131 patients treated with a standard wedged 3D technique for postoperative treatment of whole breast, according to breast size and supraclavicular node irradiation. Following dosimetric parameters were used for the comparison: D(max), D(min), D(mean), V(95%) and V(107%) for the irradiated volume; D(max), D(mean), V(80%) and V(95%) for the ipsilateral lung; D(max), D(mean), V(80%) and V(95%) for the heart. Stratification was made according to breast size and supraclavicular (SCV) nodal irradiation. As respect to irradiated volume, a significant reduction of V(107%) (mean values: 7.0 ± 6.6 versus 2.4 ± 3.7, p < 0.001) and D(max) (mean % values: 111.2 ± 2.7 versus 107.7 ± 6.3, p < 0.001), and an increase of D(min) (mean % values: 65.0 ± 17.4 versus 74.9 ± 12.9, p < 0.001) were observed with forward IMRT. The homogeneity of dose distribution to target volume significantly improved with forward IMRT in all patient groups, irrespective of breast size or supraclavicular nodal irradiation. When patients treated with supraclavicular nodal irradiation were excluded from the analysis, forward IMRT slightly reduced V(80%) (mean values: 3.7 ± 2.6 versus 3.0 ± 2.4, p = 0.03) and V(95%) (mean values 1.9 ± 1.8 versus 1.2%± 1.5; p = 0.001) of the ipsilateral lung. The dose to the heart tended to be lower with IMRT but this difference was not statistically significant. Tangential forward IMRT in postoperative treatment of whole breast improved dosimetric parameters in terms of homogeneity of dose distribution to the target in a large sample of patients, independent of breast size or supraclavicular nodal irradiation. Lung irradiation was slightly reduced in patients not undergoing to supraclavicular irradiation.