S. Fersino

Dose–volume-related dysphagia after constrictor muscles definition in head and neck cancer intensity-modulated radiation treatment

OBJECTIVE Dysphagia remains a side effect influencing the quality of life of patients with head and neck cancer (HNC) after radiotherapy. We evaluated the relationship between planned dose involvement and acute and late dysphagia in patients with HNC treated with intensity-modulated radiation therapy (IMRT), after a recontouring of constrictor muscles (PCs) and the cricopharyngeal muscle (CM). METHODS Between December 2011 and December 2013, 56 patients with histologically proven HNC were treated with IMRT or volumetric-modulated arc therapy. The PCs and CM were recontoured. Correlations between acute and late toxicity and dosimetric parameters were evaluated. End points were analysed using univariate logistic regression. RESULTS An increasing risk to develop acute dysphagia was observed when constraints to the middle PCs were not respected [mean dose (Dmean) ≥50 Gy, maximum dose (Dmax) >60 Gy, V50 >70% with a p = 0.05]. The superior PC was not correlated with acute toxicity but only with late dysphagia. The inferior PC was not correlated with dysphagia; for the CM only, Dmax >60 Gy was correlated with acute dysphagia ≥ grade 2. CONCLUSION According to our analysis, the superior PC has a major role, being correlated with dysphagia at 3 and 6 months after treatments; the middle PC maintains this correlation only at 3 months from the beginning of radiotherapy, but it does not have influence on late dysphagia. The inferior PC and CM have a minimum impact on swallowing symptoms. ADVANCES IN KNOWLEDGE We used recent guidelines to define dose constraints of the PCs and CM. Two results emerge in the present analysis: the superior PC influences late dysphagia, while the middle PC influences acute dysphagia.

Can Elderly Patients With Newly Diagnosed Glioblastoma be Enrolled in Radiochemotherapy Trials

Objectives:Age is an unfavorable prognostic factor in glioblastoma multiforme (GBM). To assess the possibility and the advantage of radiotherapy (RT) plus concomitant/sequential temozolomide (TMZ) in patients over 65 years with GBM, we analyzed 4 prospective trials in terms of compliance and outcomes. Methods:Elderly patients with histologically proven GBM, included in 4 prospective phase II studies with a Karnofsky Performance Status (KPS) >70 and a Charlson Comorbidity Index (CCI) <3, were selected for these analyses. Patients were treated by 3D-conformal RT (60 Gy), fractionated stereotactic conformal-RT (69.4 Gy), or intensity-modulated RT with simultaneous integrated boost (63 Gy). Concomitant (standard modality, first and last week, or from the Monday to Friday) and adjuvant chemotherapy with TMZ was administered. To stratify patients, recursive partitioning analysis was used. Safety and tolerability were measured by the National Cancer Institute Common Criteria. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Results:From 2001 to 2011, 201 patients were enrolled in 4 trials and 111 elderly patients were recruited for this analysis. Compliance was 96.4%: 4/111 patients discontinued treatment, prevalently for disease progression. During radiochemotherapy, acute toxicity was mild. At a median follow-up of 64 months (range, 9 to 122 mo), median PFS and OS were 10 and 13 months, respectively. Extent of surgery (P=0.009) and radiation dose (P=0.01) significantly improved survival. Conclusions:Radiochemotherapy is effective and well tolerated by elderly patients when KPS >70 and CCI <3; therefore these criterions should be considered to enroll elderly patients in combined prospective study.

Intensity modulated radiation therapy with simultaneous integrated boost in early breast cancer irradiation. Report of feasibility and preliminary toxicity.

PURPOSE To investigate the feasibility and tolerance in the use of adjuvant intensity modulated radiation therapy (IMRT) and simultaneous integrated boost in patients with a diagnosis of breast cancer after breast-conserving surgery. PATIENTS AND METHODS Between September 2011 to February 2013, 112 women with a diagnosis of early breast cancer (T1-2, N0-1, M0) were treated with IMRT and simultaneous integrated boost after breast-conserving surgery in our institution. A dose of 50Gy in 25 fractions was prescribed to the whole breast and an additional dose of radiation was prescribed on the tumour bed. A dose prescription of 60Gy in 25 fractions to the tumour bed was used in patients with negative margins after surgery, whereas if the margins were close (<1mm) or positive (without a new surgical resection) a dose of 64Gy was prescribed. All patients were followed with periodic clinical evaluation. Acute and late toxicity were scored using the EORTC/RTOG radiation morbidity score system. Both patient and physician recorded cosmetic outcome evaluation with a subjective judgment scale at the time of scheduled follow-up. RESULTS The median follow-up was 28 months (range 24-40 months). The acute skin grade toxicity during the treatment was grade 0 in 8 patients (7%), grade 1 in 80 (72%), grade 2 in 24 cases (21%). No grade 3 or higher acute skin toxicity was observed. At 12 months, skin toxicity was grade 0 in 78 patients (70%), grade 1 in 34 patients (30%). No toxicity grade 2 or higher was registered. At 24 months, skin toxicity was grade 0 in 79 patients (71%), grade 1 in 33 patients (29%). No case of grade 2 toxicity or higher was registered. The pretreatment variables correlated with skin grade 2 acute toxicity were adjuvant chemotherapy (P=0.01) and breast volume ≥700cm(3) (P=0.001). Patients with an acute skin toxicity grade 2 had a higher probability to develop late skin toxicity (P<0.0001). In the 98% of cases, patients were judged to have a good or excellent cosmetic outcome. The 2-year-overall survival and 2-year-local control were 100%. CONCLUSION These data support the feasibility and safety of IMRT with simultaneous integrated boost in patients with a diagnosis of early breast cancer following breast-conserving surgery with acceptable acute and late treatment-related toxicity. A longer follow-up is needed to define the efficacy on outcomes.

Predictors of mucositis in oropharyngeal and oral cavity cancer in patients treated with volumetric modulated radiation treatment: A dose–volume analysis

The purpose of this study was to assess predictors of mucositis in oropharyngeal and oral cavity cancer after definitive or adjuvant volumetric modulated arc radiotherapy (VMAT) +/− chemotherapy.

Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study

Background:The aim of the present study is to evaluate the impact of metastases-directed stereotactic body radiotherapy in two groups of oligometastatic prostate cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant PC (oligo-CRPC).Methods:Inclusion criteria of the present multicentre retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1–3 lesions (bone or nodes) detected with choline positron emission tomography or CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as metastases (bone or nodes) detected after a prostatic-specific antigen rise during androgen deprivation therapy (ADT). Primary end points were: distant progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC patients.Results:About 100 patients with oligorecurrent PC (139 lesions) and 41 with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1- and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were 43.2 and 21.6%. Limitations include the retrospective design.Conclusions:Stereotactic body radiotherapy seems to be a useful treatment both for oligorecurrent and oligo-CRPC.

Impact of 18F-Choline PET/CT in the Decision-Making Strategy of Treatment Volumes in Definitive Prostate Cancer Volumetric Modulated Radiation Therapy.

Introduction Aim of the study is to evaluate the impact of Cho-PET/CT in decision-making strategy of patients with localized prostate cancer (PC) eligible to definitive radiotherapy (RT). Materials and Methods Sixty patients Cho-PET/CT before RT were prospectively enrolled. All patients were treated with volumetric modulated arc therapy with simultaneous integrated boost in 28 fractions. Androgen deprivation therapy was prescribed according to National Comprehensive Cancer Network (NCCN) risk classification. Therapeutic strategy based on the Cho-PET/CT evaluation was compared with the strategy that would have been proposed in case of PET not available and/or not strictly indicated, according to international and national PC guidelines. Results Cho-PET/CT was positive in 57 cases (95%): T in 45 (79%); T in combination with N in 8 (14%); and M (bone) in combination with T or N, or both, in 4 (7%). After Cho-PET/CT, patients were stratified as follows: 26 (43%) low risk, 10 (16%) intermediate risk, and 24 (41%) high risk. Cho-PET/CT shifted treatment indication in 13 cases (21%). The changes regarding radiation treatment volumes were as follows: 6 intermediate risk (10%) shifted to high risk and consequently were irradiated on prostate, seminal vesicles, and pelvic nodes PTVs; in 7 high risk (11%), the Cho-PET/CT showed bone and/or N uptake, and consequently, a simultaneous integrated boost on PET positive sites was prescribed. Conclusions Cho-PET/CT seems to be a promising diagnostic tool in patients who are candidates for radical RT and supporting the decision making in treatment planning, in particular in intermediate-high risk.

Volumetric-modulated arc stereotactic body radiotherapy for prostate cancer: dosimetric impact of an increased near-maximum target dose and of a rectal spacer

OBJECTIVE In volumetric-modulated arc therapy (VMAT) prostate stereotactic body radiotherapy (SBRT), dose coverage of the planning target volume (PTV) becomes challenging when the sparing of rectum, bladder and urethra is strictly pursued. Our current 35-Gy-in-five-fraction plans only assure 33.2 Gy to ≥95% PTV ([Formula: see text] ≥ 95%). Looking for an improved [Formula: see text], increased near-maximum target dose (D2%) and prostate-rectum spacer insertion were tested. METHODS For 11 patients, two VMAT plans, with D2% ≤ 37.5 Gy (Hom) or D2% ≤ 40.2 Gy (Het), on each of two CT studies, before or after spacer insertion, were computed. All plans assured [Formula: see text] ≥95%, and <1 cm(3) of rectum, bladder and urethra receiving ≥35 Gy. By hypothesis testing, several dose-volume metrics for target coverage and rectal sparing were compared across the four groups of plans. The impact of spacer insertion on the fractions of rectum receiving more than 18, 28 and 32 Gy ([Formula: see text]) was further tested by linear correlation analysis. RESULTS By hypothesis testing, the increased D2% was associated with improvements in target coverage, whereas spacer insertion was associated with improvements in both target coverage and rectal [Formula: see text]. By linear correlation analysis, spacer insertion was related to the reductions in rectal [Formula: see text] for X ≥ 28 Gy. CONCLUSION A slightly increased D2% or the use of spacer insertion was each able to improve [Formula: see text]. Their combined use assured [Formula: see text] ≥ 98% to all our patients. Spacer insertion was further causative for improvements in rectal sparing. ADVANCES IN KNOWLEDGE For VMAT plans in prostate SBRT, the distinct dosimetric usefulness of increased D2% and of the use of spacer insertion were validated in terms of target coverage and rectal sparing.

Radiotherapy in patients with connective tissue diseases

The decision to offer radiotherapy in patients with connective tissue diseases continues to be challenging. Radiotherapy might trigger the onset of connective tissue diseases by increasing the expression of self-antigens, diminishing regulatory T-cell activity, and activating effectors of innate immunity (dendritic cells) through Toll-like receptor-dependent mechanisms, all of which could potentially lead to breaks of immune tolerance. This potential risk has raised some debate among radiation oncologists about whether patients with connective tissue diseases can tolerate radiation as well as people without connective tissue diseases. Because the number of patients with cancer and connective tissue diseases needing radiotherapy will probably increase due to improvements in medical treatment and longer life expectancy, the issue of interactions between radiotherapy and connective tissue diseases needs to be clearer. In this Review, we discuss available data and evidence for patients with connective tissue diseases treated with radiotherapy.

Personalized--Not Omitted--Radiation Oncology for Breast Cancer.

TO THE EDITOR: The article by Bellon 1 reports that radiation therapy (RT) for breast cancer (BC) could be omitted for patients who are unlikely to benefit from locoregional therapy. In fact, an absolute improvement of local control less than 10% correlated with a BC mortality benefit of only 0.1%. Moreover, in the editorial, RT was described as being inconvenient because of toxicity. We appreciated that it was highlighted that no data supported the omission of RT after breast-conserving surgery (BCS) and that this possibility remains only speculative. In fact, the recent meta-analysis conducted by the Early Breast Cancer Trialists’ Collaborative Group 2 showed that, during the next 15 years, approximately one death from BC would be avoided for every four local recurrences avoided. It is well recognized that killing of locoregional microscopic tumor foci reduces the potential risk of local recurrences and distant metastasis. 2 Regarding the possibility of omitting RT in selected patients with BC without definitive data, several questions could emerge. First, can we omit a local treatment if it does not increase overall survival? In other cancer diseases, such as rectal cancer, the standard conservative treatment approach, including RT, reduces the risk of locoregional recurrences without increasing overall survival. To our knowledge, the omission of RT has never been discussed. Undoubtedly, the reduction of local recurrences improve quality of life for patients with BC. In European Organisation for Research and Treatment of Cancer (EORTC) trial 10801, BCS with RT was associated with a better body image compared with a mastectomy approach. 3 Second, considering the increased risk of local failure when RT is omitted, shall we consider more intensive follow-up? Two randomized trials did not show any effect of intensive diagnostic follow-up on 5- and 10-year mortality for patients with primary BC treated with BCS and RT. 4,5 Therefore, these data are no longer reliable if RT is not performed, and, probably, intensive follow-up should be proposed to patients to prevent local recurrence, increasing health care system costs.

Cone-beam computed tomography in lung stereotactic ablative radiation therapy: predictive parameters of early response.

OBJECTIVE: To analyze lung lesion volume variations by contouring on cone-beam CT (CBCT) images to evaluate the early predictive parameters of stereotactic ablative radiation therapy (SABR) treatment response. METHODS: The prescribed dose of SABR was varied according to the tumour site (central or peripheral) and maximum diameter of the lesions by using a strategy of risk-adapted dose prescription with a dose range between 48 and 70 Gy in 3-10 consecutive fractions. For the purpose of the analysis, the gross tumour volume (GTV) was recontoured for each patient at first and last CBCT using two lung levels/windows: (a) -600/1000 HU and (b) -1000/250 HU. Univariate analysis was performed to evaluate a correlation between lung lesion variations on CBCT using the two levels/windows and treatment response 6 months after SABR. Independent variables were the number of fractions, time between initial and final fraction, biologically effective dose and pre-SABR GTV. Cut points of lesion volume reduction were evaluated to determine the correlation with complete response 6 months after SABR. RESULTS: 41 lung lesions were evaluated. 82 lung lesions were recontoured for each CBCT level/window. A lung lesion shrinkage of at least 20% was revealed to be statistically related to complete response 6 months after SABR for both the CBCT levels/windows used. The probability of complete response ranged between six and eight times higher in respect to CBCT levels/windows -600/1000 HU and -1000/250 HU, respectively, compared with patients without a lesion shrinkage of 20% at the last session of SABR. CONCLUSION: According to current findings, a lung lesion shrinkage of at least 20% at the last session of SABR could be predictable of complete response 6 months thereafter. Further investigations about this topic are needed. ADVANCES IN KNOWLEDGE: Prediction of the early tumour response could be useful to personalize imaging restaging after the completion of SABR or to incorporate additional therapies in case of poor responders to improve clinical outcomes.