Stereotactic partial breast irradiation in primary breast cancer: A comprehensive review of the current status and future directions.

In selected low-risk breast cancer patients, accelerated partial breast irradiation (APBI) may represent an alternative option to the whole breast irradiation to reduce the volume of irradiated breast and total treatment duration. In the last few years, preliminary data from clinical trials showed that stereotactic partial breast radiotherapy may have the advantage to be less invasive compared to other APBI techniques, with preliminary good results in terms of local toxicity and cosmesis: the use of magnetic resonance, fiducial markers in the tumor bed, and new breast devices support both a precise definition of the target and radiation planning. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021257856, identifier CRD42021257856.

Validation of a biomarker tool capable of measuring the absorbed dose soon after exposure to ionizing radiation.

A radiological or nuclear attack could involve such a large number of subjects as to overwhelm the emergency facilities in charge. Resources should therefore be focused on those subjects needing immediate medical attention and care. In such a scenario, for the triage management by first responders, it is necessary to count on efficient biological dosimetry tools capable of early detection of the absorbed dose. At present the validated assays for measuring the absorbed dose are dicentric chromosomes and micronuclei counts, which require more than 2-3 days to obtain results. To overcome this limitation the NATO SPS Programme funded an Italian-Egyptian collaborative project aimed at validating a fast, accurate and feasible tool for assessing the absorbed dose early after radiation exposure. Biomarkers as complete blood cell counts, DNA breaks and radio-inducible proteins were investigated on blood samples collected before and 3 h after the first fraction of radiotherapy in patients treated in specific target areas with doses/fraction of about: 2, 3.5 or > 5 Gy and compared with the reference micronuclei count. Based on univariate and multivariate multiple linear regression correlation, our results identify five early biomarkers potentially useful for detecting the extent of the absorbed dose 3 h after the exposure.

Short course hypofractionated whole breast irradiation after conservative surgery: a single institution phase II study.

BACKGROUND: To assess the oncologic outcomes of hypofractionated whole breast irradiation (Hypo-WBI). METHODS: Eligible patients had undergone breast conservative surgery for early breast cancer (pTis-2) and none/limited nodal involvement. Hypo-WBI consisted of 34 Gy in 10 daily fractions over 2 weeks to the whole breast three-dimensional conformal radiotherapy (3DCRT), followed by a single fraction of 8 Gy to the tumor bed after 1 week (electrons). Primary endpoint is freedom from ipsilateral breast tumor recurrence (IBTR). Minimum follow up for living & event-free patients is 3 yrs.; median follow up time of the whole analyzed patient population is 5.4 yrs. (range: 1.8-11.4 yrs). RESULTS: Two hundred fifty-one patients were accrued from 2004 to 2013. All patients underwent local excision of the primary tumor to negative margins. Four patients failed in the ipsilateral breast after a median time of 3.2 years (range: 1.7-5.7 yrs) for a 5-year IBTR-free survival of 98.7% (95%CI: 97.3%-100%). IBTR-free survival was significantly higher for patients with invasive cancer than for patients with intraductal carcinoma (p = 0.036). Within patients with invasive tumors, no clear trends or associations were detected between IBTR and age, grading, molecular subtype, pT or pN stage. At 5 years, the actuarial rates of GR2 fibrosis and GR2+ teleangectasia are 2.4% (95%CI: 0-6.5%) and 7.1% (95%CI: 0.4-13.7%), respectively. Cosmesis was scored as excellent/good by ≈95% of patients and ≈60% of clinicians. CONCLUSIONS: Hypo-WBI in 3 weeks allows excellent oncologic outcomes for invasive breast cancer after conservative surgery. Patients with intraductal carcinoma should be treated with Hypo-WBI only within a controlled study. TRIAL REGISTRATION: IRE-IFO Ethical and Scientific Committee (cod. RS61/04).

Double-blind randomized phase III study comparing a mixture of natural agents versus placebo in the prevention of acute mucositis during chemoradiotherapy for head and neck cancer.

BACKGROUND: There is no widely accepted intervention in the prevention of acute mucositis during chemoradiotherapy for head and neck carcinoma. In the present double-blind study, we tested 4 natural agents, propolis, aloe vera, calendula, and chamomile versus placebo. METHODS: Patients undergoing concomitant chemo-intensity-modulated radiotherapy (IMRT) were given natural agent or matched placebo; grade 3 mucositis on physical examination according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was the primary endpoint. Various covariates were tested at logistic regression, including the individual amount of mucosa receiving at least 9.5 Gy per week (V9.5w). RESULTS: One hundred seven patients were randomized from January 2011 to July 2014, and 104 were assessable (51%-49% were assigned to the placebo group and 53%-51% were assigned to the natural agent). Overall, 61 patients developed peak grade 3 mucositis with no difference between arms (P = .65). Conversely, V9.5w (P = .007) and primary site (P = .037) were independent predictors. CONCLUSION: The selected natural agents do not prevent mucositis, whereas the role of V9.5w is confirmed.

Detection of ATM germline variants by the p53 mitotic centrosomal localization test in BRCA1/2-negative patients with early-onset breast cancer.

BACKGROUND: Variant ATM heterozygotes have an increased risk of developing cancer, cardiovascular diseases, and diabetes. Costs and time of sequencing and ATM variant complexity make large-scale, general population screenings not cost-effective yet. Recently, we developed a straightforward, rapid, and inexpensive test based on p53 mitotic centrosomal localization (p53-MCL) in peripheral blood mononuclear cells (PBMCs) that diagnoses mutant ATM zygosity and recognizes tumor-associated ATM polymorphisms. METHODS: Fresh PBMCs from 496 cancer patients were analyzed by p53-MCL: 90 cases with familial BRCA1/2-positive and -negative breast and/or ovarian cancer, 337 with sporadic cancers (ovarian, lung, colon, and post-menopausal breast cancers), and 69 with breast/thyroid cancer. Variants were confirmed by ATM sequencing. RESULTS: A total of seven individuals with ATM variants were identified, 5/65 (7.7 %) in breast cancer cases of familial breast and/or ovarian cancer and 2/69 (2.9 %) in breast/thyroid cancer. No variant ATM carriers were found among the other cancer cases. Excluding a single case in which both BRCA1 and ATM were mutated, no p53-MCL alterations were observed in BRCA1/2-positive cases. CONCLUSIONS: These data validate p53-MCL as reliable and specific test for germline ATM variants, confirm ATM as breast cancer susceptibility gene, and highlight a possible association with breast/thyroid cancers.

Prevalence of Cardiovascular Disease and Osteoporosis During Androgen Deprivation Therapy Prescription Discordant to EAU Guidelines: Results From a Multicenter, Cross-sectional Analysis From the CHOsIng Treatment for Prostate canCEr (CHOICE) Study.

OBJECTIVE: To analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines. MATERIALS AND METHODS: The CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected. According to EAU guidelines, the cohort was categorized in discordant ADT (Group A) and concordant ADT (Group B). The prevalence of CVD and osteoporosis after ADT was recorded. RESULTS: The final cohort included 1075 patients. According to EAU guidelines adherence, 285 (26.51%) and 790 (73.49%) were considered discordant and concordant, respectively. The proportion of men with Charlson Comorbidity Index > 2 at baseline was statistically similar in Group A (81.8%) compared to Group B (80.8%) (P = .96). The number of complications reported at enrollment was as follows: cardiovascular in 351 (32.7%), endocrine in 166 (15.4%), sexual in 498 (46.3%), osteoporosis in 181 (16.8%), and gynecomastia in 274 (25.5%) subjects. At the multivariate logistic regression analysis adjusted for confounding factors, discordant ADT was associated with greater risk of cardiovascular complications (odds ratio: 2.07; P < .01) and osteoporosis (odds ratio: 1.75; P = .04). CONCLUSION: About one-third of patients with PCa received inappropriate ADT and showed a greater risk of CVD and osteoporosis. These results could be useful for setting better policy strategies to limit the inappropriateness of ADT prescription.

Efficacy and mucosal toxicity of concomitant chemo-radiotherapy in patients with locally-advanced squamous cell carcinoma of the head-and-neck in the light of a novel mathematical model.

BACKGROUND: In the last several decades, combined radiotherapy (RT) and chemotherapy (CT) have been recognized as feasible in locally-advanced-squamous-cell-carcinoma of the head-and-neck (LA-HNSCC). Several meta-analyses identified concurrent RT+CT (CRT) most likely effective approach respect to RT-alone. However, radiobiological models comparing different chemotherapeutic schedules against delivered RT fractionation schedule for overall survival and toxicity are still needed. METHODS AND MATERIALS: Based on 9 randomized trials (2785 patients), radiobiological models and multivariate logistic regression model were used to derive dose-response curves and estimate the 5-year-overall survival (OS) and ≥G3 acute mucositis rate of CRT or RT-alone. RESULTS: Equivalent dose at 2 Gy/fraction (EQD2) was calculated using the linear quadratic model. The effect of CRT schedules, considering the CT type and its administration schedule and the HPV status of tumors were estimated using the univariate/multivariate logistic regression. The multivariate logistic regression model for 5y-OS indicated EQD2 and the type of CT, the chemo-sensitization fraction and the HPV status significant prognostic factors, while for toxicity both EQD2 and the concomitant administration of 5-fluorouracil (5Fu) resulted as significant prognostic factors. Combined schedules cisplatin (DDP)+/-5Fu+RT produced the higher OS compared with combined carboplatin+/-5Fu+RT or RT-alone. The concomitant administration of Fu and schedule with high EQD2 increase the rate of observed ≥G3 acute mucositis. CONCLUSION: Multivariate logistic regression models can be used to predict CRT effect in terms of OS and ≥G3-mucositis, contributing to the identification of novel treatment schedules.

Impact of Sequencing Radiation Therapy and Chemotherapy on Long-Term Local Toxicity for Early Breast Cancer: Results of a Randomized Study at 15-Year Follow-Up.

PURPOSE: To compare long-term late local toxicity after either concomitant or sequential chemoradiation therapy after breast-conserving surgery. METHODS AND MATERIALS: From 1997 to 2002, women aged 18 to 75 years who underwent breast-conserving surgery and axillary dissection for early breast cancer and in whom CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy was planned were randomized between concomitant and sequential radiation therapy. Radiation therapy was delivered to the whole breast through tangential fields to 50 Gy in 20 fractions over a period of 4 weeks, followed by an electron boost. Surviving patients were tentatively contacted and examined between March and September 2014. Patients in whom progressive disease had developed or who had undergone further breast surgery were excluded. Local toxicity (fibrosis, telangiectasia, and breast atrophy or retraction) was scored blindly to the treatment received. A logistic regression was run to investigate the effect of treatment sequence after correction for several patient-, treatment-, and tumor-related covariates on selected endpoints. The median time to cross-sectional analysis was 15.7 years (range, 12.0-17.8 years). RESULTS: Of 206 patients randomized, 154 (74.8%) were potentially eligible. Of these, 43 (27.9%) refused participation and 4 (2.6%) had been lost to follow-up, and for 5 (3.2%), we could not restore planning data; thus, the final number of analyzed patients was 102. No grade 4 toxicity had been observed, whereas the number of grade 3 toxicity events was low (<8%) for each item, allowing pooling of grade 2 and 3 events for further analysis. Treatment sequence (concomitant vs sequential) was an independent predictor of grade 2 or 3 fibrosis according to both the National Cancer Institute Common Terminology Criteria for Adverse Events (odds ratio [OR], 4.05; 95% confidence interval [CI], 1.34-12.2; P=.013) and the SOMA (Subjective, Objective, Management and Analytic) scale (OR, 3.75; 95% CI, 1.19-11.79; P=.018), as well as grade 2 or 3 breast atrophy or retraction (OR, 3.87; 95% CI, 1.42-10.56; P=.008). No effect on telangiectasia was detected. CONCLUSIONS: At long-term follow-up, concomitant chemoradiation therapy has a detrimental effect on both fibrosis and retraction with an approximately 4-fold increase in the odds of grade 2 or 3 toxicity.

Patterns of prescription and adherence to European Association of Urology guidelines on androgen deprivation therapy in prostate cancer: an Italian multicentre cross-sectional analysis from the Choosing Treatment for Prostate Cancer (CHOICE) study.

OBJECTIVE: To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription. METHODS: The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B). RESULTS: The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT. CONCLUSION: EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk.

Intensity-modulated pelvic radiation therapy and simultaneous integrated boost to the prostate area in patients with high-risk prostate cancer: a preliminary report of disease control.

The aim of the study was to report the clinical results in patients with high-risk prostate cancer treated with pelvic intensity-modulated radiation therapy (IMRT) and simultaneous integrated boost (SIB) to the prostate area. A total of 110 patients entered our study, 37 patients presented with localized prostate cancer and radiological evidence of node metastases or ≥15% estimated risk of lymph node (LN) involvement, while 73 patients underwent postoperative adjuvant or salvage irradiation for biochemical or residual/recurrent disease, LN metastases, or high risk of harboring nodal metastases. All patients received androgen deprivation therapy (ADT) for 2 years. The median follow-up was 56.5 months. For the whole patient group, the 3- and 5-year freedom from biochemical failure were 82.6% and 74.6%, respectively, with a better outcome in patients treated with radical approach. The 3- and 5-year freedom from local failure were 94.4% and 90.2%, respectively, while the 3- and 5-year distant metastasis-free survival were 87.8% and 81.7%, respectively. For all study patients, the rate of freedom from G2 acute rectal, intestinal, and urinary toxicities was 60%, 77%, and 61%, respectively. There was no G3 acute toxicity, ≥G2 late intestinal toxicity, or G3 late urinary or rectal toxicity. The 3- and 5-year ≥G2 freedom from late rectal toxicity rate were 98% and 95%, respectively, while the 3- and 5-year ≥G2 freedom from late urinary toxicity rate were 95% and 88%, respectively. The study concludes that pelvic IMRT and SIB to the prostatic area in association with 2-year ADT was a well-tolerated technique, providing high disease control in patients with prostate cancer requiring LN treatment.

Dose escalation using ultra-high dose IMRT in intermediate risk prostate cancer without androgen deprivation therapy: preliminary results of toxicity and biochemical control.

BACKGROUND: To investigate the feasibility of dose escalation (86 Gy at 2 Gy/fraction) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer without androgen deprivation therapy. METHODS: Patients with histologically proven adenocarcinoma of the prostate, intermediate prognostic category, were enrolled in this study. Early and late toxicity were scored according to the Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0. Treatment outcome was stated in terms of biochemical failure, biopsy result and clinical failure. RESULTS: 39 patients with a median follow-up of 71 months were analyzed. No patient experienced G3 or G4 acute gastrointestinal (GI) or genitourinary (GU) toxicity. G2 acute GI and GU toxicity were observed in 17 (44%) and 20 (51%) patients, respectively. Fourteen patients (36%) did not experience acute GI toxicity and 4 patients (10%) did not experience acute GU toxicity. G2 late GI bleeding occurred in 7 of 39 patients (18%). Both G3 and G4 late GI toxicity were seen only in one patient (2.5%). Two patients (5%) experienced G2 late GU toxicity, while G3 late GU toxicity occurred in 3 patients (8%). The 5-year actuarial freedom from biochemical failure (FFBF) was 87%. Thirty-four patients (87%) did not show biochemical relapse. Seventeen patients (44%) underwent biopsy two year after radiotherapy; of these only two were non-negative and both did not show evidence of biochemical disease. CONCLUSIONS: IMRT treatment of patients with localized intermediate-risk prostate cancer at high dose levels without using androgen deprivation therapy (ADT) seems to give good disease control. Nevertheless, future trials should aim at further decreasing toxicity by exploiting image guidance techniques and by reducing the dose delivered at the interface between organs at risk and prostate.

The role of radiotherapy in bladder cancer.

In this article we report on the current role of radiotherapy in the management of non-muscle invasive as well as in muscle invasive bladder cancer.
Radiotherapy seems to have no role in non-muscle invasive bladder cancer.
In muscle invasive bladder tumors, the role of radiotherapy is under investigation in view of new radiotherapy techniques and novel cytotoxic and biological agents.

Evidence from a breast cancer hypofractionated schedule: late skin toxicity assessed by ultrasound.

BACKGROUND: Feasibility of whole breast hypofractionated radiotherapy schedules in breast conserving therapy is recognized however concerns remain about the role of the boost dose on the overall treatment's potential toxicity. In this study we report on the possibility to quantitatively evaluate radiation induced toxicity in patients treated with an abbreviated course with major concern in the irradiated boost region. METHODS: Eighty-nine patients who underwent conservative surgery for early-stage breast cancer followed by adjuvant accelerated hypofractionated whole breast radiotherapy were included in this study to assess skin and subcutaneous tissue late toxicity by means of ultrasonographic quantitative examination. For each patient the skin thickness was measured at four positions: on the irradiated breast, in the boost region and in the corresponding positions in the contra-lateral not treated breast. All patients were scanned by the same radiologist to reduce potential inter-operator variability, the operator was blind to the scoring of the patient CTCv3 late toxicity as well as patient treatment characteristics. Ultrasound assessment and clinical evaluation were compared. RESULTS: The median time between the end of adjuvant radiotherapy and ultrasound examination was 20.5 months. The measured mean skin thickness in the irradiated breast was 2.13 ± 0.72 mm while in the mirror region of the contra-lateral healthy breast was 1.61 ± 0.29 mm. The measured mean skin thickness in the irradiated boost region was 2.25 ± 0.79 mm versus 1.63 ± 0.33 mm in the corresponding region of contra-lateral healthy breast. The mean increment in skin thickness respect to the counterpart in the healthy breast was 0.52 ± 0.67 mm and 0.62 ± 0.74 mm for the breast and the boost region respectively. A significant direct correlation was found between the increment in skin thickness in the irradiated breast and in the boost region with fibrosis (G ≥ 1). CONCLUSIONS: In this study results from a breast cancer hypofractionated schedule in terms of late skin toxicity are reported. In particular our study confirms that late cutaneous reactions can be reliably assed by ultrasonographic examination, also discriminating between regions irradiated at different doses, and that this instrumental evaluation is in agreement with clinical stated toxicity.

Dosimetric and clinical advantages of deep inspiration breath-hold (DIBH) during radiotherapy of breast cancer.

BACKGROUND: To investigate the potential dosimetric and clinical benefits of Deep Inspiration Breath-Hold (DIBH) technique during radiotherapy of breast cancer compared with Free Breathing (FB). METHODS: Eight left-sided breast cancer patients underwent a supervised breath hold during treatment. For each patient, two CT scans were acquired with and without breath hold, and virtual simulation was performed for conventional tangential fields, utilizing 6 or 15 MV photon fields. The resulting dose-volume histograms were calculated, and the volumes of heart/lung irradiated to given doses were assessed. The left anterior descending coronary artery (LAD) mean and maximum doses were calculated, together with tumour control probability (TCP) and normal tissue complication probabilities (NTCP) for lung and heart. RESULTS: For all patients a reduction of at least 16% in lung mean dose and at least 20% in irradiated pulmonary volumes was observed when DIBH was applied. Heart and LAD maximum doses were decreased by more than 78% with DIBH. The NTCP values for pneumonitis and long term cardiac mortality were also reduced by about 11% with DIBH. The NTCP values for pericarditis were zero for both DIBH and FB. CONCLUSION: Delivering radiation in DIBH conditions the dose to the surrounding normal structures could be reduced, in particular heart, LAD and lung, due to increased distance between target and heart, and to reduced lung density.

Development and optimization of a beam shaper device for a mobile dedicated IOERT accelerator.

PURPOSE: The aim of this study was to design and build a prototype beam shaper to be used on a dedicated mobile accelerator that protects organs at risk within the radiation field and conforms the beam to the target geometry during intraoperative electron radiotherapy (IOERT). A dosimetric characterization of the beam shaper device was performed based on Monte Carlo (MC) simulations, as well as experimental data, at different energies, field sizes, and source to skin distances. METHODS: A mobile light intraoperative accelerator (LIAC(®), Sordina, Italy) was used. The design of the beam shaper prototype was based on MC simulations (BEAMnrc∕OMEGA and DOSXYZnrc code) for a selection of materials and thicknesses, as well as for dosimetric characterization. Percentage depth dose (PDD) and profile measurements were performed using a p-type silicon diode and a commercial water phantom, while output factors were measured using a PinPoint ion chamber in a PMMA phantom. Planar doses in planes of interest were carried out using radiochromic films (Gafchromic(TM) EBT and EBT2) in PMMA and in a Solid Water(®) phantom. Several experimental set-ups were investigated with the beam shaper device fixed on the top of the phantom, varying both the short side of the rectangular field and the air gap between the device and the phantom surface, simulating the clinical situation. The output factors (OFs) were determined using different geometrical set-ups and energies. RESULTS: The beam shaper prototype consists of four blades sliding alongside each other and mounted on a special support at the end of the 10 cm diameter PMMA circular applicator. Each blade is made of an upper layer of 2.6 cm of Teflon(®) and a lower layer of 8 mm of stainless steel. All rectangles inscribed in a 5 cm diameter can be achieved in addition to any "squircle-shaped" field. When one side of the rectangular field is held constant and the second side is reduced, both R(50) and R(max) move towards the phantom surface. Comparing the PDDs obtained with the 5 cm circular applicator and with a 4.4 × 4.4 cm(2) square field (that is the equivalent square of the 5 cm circular field) obtained with the beam shaper, a different behavior was observed in the region extending from the surface to a depth of 50% of the maximum dose. Isodoses measured for rectangular fields used for clinical cases (i.e., 4 × 9 cm(2) 8 MeV) are shown, with different air gaps. For each energy investigated, the normalized OFs slowly increase, when the length of the side decreases down to about 4 cm, and then rapidly decreases for smaller field widths. MC simulation showed an excellent agreement with experimental data (<2%). CONCLUSIONS: The beam shaper device is able to provide square∕rectangular∕squircle fields with adequate dose homogeneity for mobile dedicated accelerators, thus allowing conformal treatment with IOERT. Monte Carlo simulation can be a very useful tool to simulate any clinical set up and can be used to create a data set to calculate MUs, thereby increasing the accuracy of the delivered dose during IOERT procedures.

A new model for predicting acute mucosal toxicity in head-and-neck cancer patients undergoing radiotherapy with altered schedules.

PURPOSE: One of the worst radiation-induced acute effects in treating head-and-neck (HN) cancer is grade 3 or higher acute (oral and pharyngeal) mucosal toxicity (AMT), caused by the killing/depletion of mucosa cells. Here we aim to testing a predictive model of the AMT in HN cancer patients receiving different radiotherapy schedules. METHODS AND MATERIALS: Various radiotherapeutic schedules have been reviewed and classified as tolerable or intolerable based on AMT severity. A modified normal tissue complication probability (NTCP) model has been investigated to describe AMT data in radiotherapy regimens, both conventional and altered in dose and overall treatment time (OTT). We tested the hypothesis that such a model could also be applied to identify intolerable treatment and to predict AMT. This AMT NTCP model has been compared with other published predictive models to identify schedules that are either tolerable or intolerable. The area under the curve (AUC) was calculated for all models, assuming treatment tolerance as the gold standard. The correlation between AMT and the predicted toxicity rate was assessed by a Pearson correlation test. RESULTS: The AMT NTCP model was able to distinguish between acceptable and intolerable schedules among the data available for the study (AUC = 0.84, 95% confidence interval = 0.75-0.92). In the equivalent dose at 2 Gy/fraction (EQD2) vs OTT space, the proposed model shows a trend similar to that of models proposed by other authors, but was superior in detecting some intolerable schedules. Moreover, it was able to predict the incidence of ≥G3 AMT. CONCLUSION: The proposed model is able to predict ≥G3 AMT after HN cancer radiotherapy, and could be useful for designing altered/hypofractionated schedules to reduce the incidence of AMT.

Updated results and patterns of failure in a randomized hypofractionation trial for high-risk prostate cancer.

PURPOSE: To report long-term results and patterns of failure after conventional and hypofractionated radiation therapy in high-risk prostate cancer. METHODS AND MATERIALS: This randomized phase III trial compared conventional fractionation (80 Gy at 2 Gy per fraction in 8 weeks) vs hypofractionation (62 Gy at 3.1 Gy per fraction in 5 weeks) in combination with 9-month androgen deprivation therapy in 168 patients with high-risk prostate cancer. Freedom from biochemical failure (FFBF), freedom from local failure (FFLF), and freedom from distant failure (FFDF) were analyzed. RESULTS: In a median follow-up of 70 months, biochemical failure (BF) occurred in 35 of the 168 patients (21%) in the study. Among these 35 patients, local failure (LF) only was detected in 11 (31%), distant failure (DF) only in 16 (46%), and both LF and DF in 6 (17%). In 2 patients (6%) BF has not yet been clinically detected. The risk reduction by hypofractionation was significant in BF (10.3%) but not in LF and DF. We found that hypofractionation, with respect to conventional fractionation, determined only an insignificant increase in the actuarial FFBF but no difference in FFLF and FFDF, when considering the entire group of patients. However, an increase in the 5-year rates in all 3 endpoints-FFBF, FFLF, and FFDF-was observed in the subgroup of patients with a pretreatment prostate-specific antigen (iPSA) level of 20 ng/mL or less. On multivariate analysis, the type of fractionation, iPSA level, Gleason score of 4+3 or higher, and T stage of 2c or higher have been confirmed as independent prognostic factors for BF. High iPSA levels and Gleason score of 4+3 or higher were also significantly associated with an increased risk of DF, whereas T stage of 2c or higher was the only independent variable for LF. CONCLUSION: Our results confirm the isoeffectiveness of the 2 fractionation schedules used in this study, although a benefit in favor of hypofractionation cannot be excluded in the subgroup of patients with an iPSA level of 20 ng/mL or less. The α/ß ratio might be more appropriately evaluated by FFLF than FFBF results, at least in high-risk disease.

SNPs in DNA repair or oxidative stress genes and late subcutaneous fibrosis in patients following single shot partial breast irradiation.

BACKGROUND: The aim of this study was to evaluate the potential association between single nucleotide polymorphisms related response to radiotherapy injury, such as genes related to DNA repair or enzymes involved in anti-oxidative activities. The paper aims to identify marker genes able to predict an increased risk of late toxicity studying our group of patients who underwent a Single Shot 3D-CRT PBI (SSPBI) after BCS (breast conserving surgery). METHODS: A total of 57 breast cancer patients who underwent SSPBI were genotyped for SNPs (single nucleotide polymorphisms) in XRCC1, XRCC3, GST and RAD51 by Pyrosequencing technology. Univariate analysis (ORs and 95% CI) was performed to correlate SNPs with the risk of developing ≥ G2 fibrosis or fat necrosis. RESULTS: A higher significant risk of developing ≥ G2 fibrosis or fat necrosis in patients with: polymorphic variant GSTP1 (Ile105Val) (OR = 2.9; 95%CI, 0.88-10.14, p = 0.047). CONCLUSIONS: The presence of some SNPs involved in DNA repair or response to oxidative stress seem to be able to predict late toxicity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01316328.

Influence of intensity-modulated radiation therapy technique on xerostomia and related quality of life in patients treated with intensity-modulated radiation therapy for nasopharyngeal cancer.

BACKGROUND: The purpose of this study was to compare 5-field and 7-field intensity-modulated radiation therapy (IMRT) techniques in terms of xerostomia and related quality of life in patients with nasopharyngeal cancer. METHODS: Eight and 23 patients were treated with 5-field (group I) and 7-field (group II) techniques, respectively. The xerostomia was evaluated using the Radiation Therapy Oncology Group (RTOG) scale, stimulated and unstimulated salivary flow (SSF/USF), and xerostomia-related questionnaires (XQs). The assessments were done before and at 3, 6, 12, 18, and 24 months after radiotherapy. RESULTS: The mean parotid dose was 45.7 Gy and 29.9 Gy and the ≥G3 toxicity at 24 months was 25% and 19% in group I and II, respectively. Sixty-three percent and 93% of patients recovered at least 25% of SSF pretherapy values. The XQ scores of both groups improved over time but more so in group II. CONCLUSION: The 7-field technique decreases the mean parotid dose, reducing xerostomia assessed by the RTOG/XQ score.