Gioacchino Di Paola

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.

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.

Stereotactic Ablative Radiation Therapy for Lung Oligometastases: Predictive Parameters of Early Response by (18)FDG-PET/CT

Objectives: The objective of this study was to investigate fludeoxyglucose F 18 positron emission tomography/computed tomography (18FDG‐PET/CT) parameters as predictive of response after stereotactic ablative radiotherapy (SABR) for lung oligometastases. Methods: The inclusion criteria of the current retrospective study were as follows: (1) lung oligometastases treated by SABR, (2) presence of 18FDG‐PET/CT before and after SABR for at least two subsequent evaluations, (3) Karnofsky performance status higher than 80, and (4) life expectancy longer than 6 months. All patients were treated with a biologically equivalent dose of at least 100 Gy with an alpha/beta ratio of 10. The following metabolic parameters were semiquantitatively defined: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume, and total lesion glycolysis. Results: A total of 50 patients met the inclusion criteria, for a total of 70 lung metastases. The pre‐SABR median SUVmax was 6.5 (range 4–17), the median SUVmean was 3.7 (range 2.5–6.5), and the median metabolic tumor volume was 2.3 cm3 (0.2–31 cm3). The following metabolic parameters were significantly related to complete response at 6 months: SUVmax less than 5 (p < 0.001) and SUVmean less than 3.5 (p = 0.03). &Dgr;SUVmax at 3 to 6 months was +126% for lesions with in‐field progression versus –26% for the remaining lesions (p = 0.002). &Dgr;SUVmean at 3 to 6 months was +15% for lesions with in‐field progression versus –26% for the remaining metastases (p = 0.008). Conclusions: In the current analysis, complete response from lung metastasis at 6 months after stereotactic body radiation therapy was significantly associated with both the maximum and mean values of pre‐SABR 18FDG‐PET/CT SUV. Longer‐term trials are strongly advocated to improve the personalization of the monitoring of tumor response in patients with lung oligometastases and, consequently, monitoring of the cost‐effectiveness of the health care.

Moderate Hypofractionated Postprostatectomy Volumetric Modulated Arc Therapy With Daily Image Guidance (VMAT-IGRT): A Mono-institutional Report on Feasibility and Acute Toxicity

Introduction The aim of this study was to evaluate the acute toxicity profiles of a moderate hypofractionated regimen with volumetric modulated arc therapy (VMAT) in patients with prostate cancer (PC) who underwent radical prostatectomy. Material and Methods From December 2012 to February 2016, 125 patients, previously having undergone radical prostatectomy, received adjuvant (64 patients) or salvage (61 patients) radiotherapy (RT) inside an institutional protocol of moderate hypofractionation schedule using the VMAT technique (Varian RapidArc, Palo Alto, CA). Eligible patients were < 85 years old, with an Eastern Cooperative Oncology Group performance status of 0 to 2, histologically proven adenocarcinoma of the prostate without distant metastases, and pathologic stage pT2‐4 N0‐1, with at least 1 of the following risk factors: capsular perforation, positive surgical margins, seminal vesicle invasion, and/or postoperative prostate‐specific antigen > 0.2 ng/mL. Patients were stratified into low (1%), intermediate (9%), and high‐risk (90%) groups. The median age was 68 years. The median doses were 66 Gy (range, 65.5‐71.4 Gy) to the prostatic bed and 52.5 Gy (range, 50.4‐54 Gy) to the pelvic lymph nodes, in 28 or 30 fractions. The acute genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Common Terminology Criteria for Adverse Events, v4. Results All 125 patients completed the planned treatment, with good tolerance. After RT, the median follow‐up was 18 months. Acute toxicities were recorded for the GU (G0, 45/125 [36%]; G1, 63/125 [50.4%]; G2, 16/125 [12.8%]; G3, 1/125 [0.8%]) and the GI (G0, 42/125 [33.6%]; G1, 72/125 [57.6%]; G2, 11/125 [8.8%]; no G3). Analyzing data according to RT intent, a higher rate of GU toxicity ≥ 2 was found in the adjuvant setting (17.1%) with respect to the salvage group (9.8%); P = .01 with the Fisher exact text. Furthermore, at statistical analysis, no difference was found between the type of surgery (robotic, laparoscopic, or open) and incidence of urinary incontinence (P = .8). The actuarial Kaplan‐Meier rates for biochemical disease‐free survival were 94% and 77% for adjuvant and salvage RT, at 36 months. Conclusions Moderate hypofractionated postoperative RT with VMAT was feasible and safe with acceptable acute GU and GI toxicities. Longer follow‐up is needed to assess late toxicity and clinical outcomes. Micro‐Abstract In prostate cancer, moderate hypofractionated postoperative radiotherapy with the volumetric modulated arc therapy technique is a promising option. Our series seems to confirm the feasibility and the good acute genitourinary and gastrointestinal toxicity profile comparable with conventional fractionation schedules. Longer follow‐up is needed to evaluate late toxicity and clinical outcomes.

Weekly Cisplatin and Volumetric-Modulated Arc Therapy With Simultaneous Integrated Boost for Radical Treatment of Advanced Cervical Cancer in Elderly Patients Feasibility and Clinical Preliminary Results

Background: To evaluate the feasibility and clinical preliminary results of weekly cisplatin and volumetric-modulated arc therapy to the pelvis with simultaneous integrated boost to macroscopic disease in a cohort of elderly patients. Materials and Methods: Inclusion criteria of this prospective study were age ≥70 years, Karnofsky performance status 70 to 100, locally advanced histologically proven squamous cervical carcinoma, and patients unable to undergo brachytherapy. Radiation doses prescribed were 66 Gy to the macroscopic disease and 54 Gy to the pelvic nodes in 30 fractions. Weekly cisplatin dose was 40 mg/mq. Results: A total of 30 patients were recruited. Median follow-up was 32 months (range: 8-48 months). Median age was 72 years (range: 70-84 years). The 3-year overall survival and local control were 93% and 80%, respectively. The median time to progression was 24 months (range: 6-30 months). Analyzing clinical outcome grouping based on the stage of disease, II versus III, the 3-year overall survival was 100% and 85%, respectively. The 3-year local control was 91% for stage II and 67% for stage III. Acute and late toxicities were acceptable without severe events. Conclusion: Weekly cisplatin and volumetric-modulated arc therapy–simultaneous integrated boost for radical treatment of advanced cervical cancer in the current cohort of elderly patients were feasible. Long-term results and prospective randomized trials are advocated.

Hippocampal dose during Linac-based stereotactic radiotherapy for brain metastases: An observational study

INTRODUCTION Aim of the present study is to evaluate homolateral and contralateral hippocampus (H-H, C-H, respectively) dose during Fractionated Stereotactic Radiotherapy (FSRT) or Radiosurgery (SRS) for brain metastases (BM). MATERIALS & METHODS Patients with BM<5, size≤30mm, KPS≥80 and a life expectancy>3months, were considered for SRS/FSRT (total dose 15-30Gy, 1-5 fractions). For each BM, a Flattening Filter Free (FFF) Volumetric Modulated Arc Therapy (VMAT) plan was generated with one or two arcs. Hippocampi were not considered during optimizations phase and were contoured and evaluated retrospectively in terms of dose: the Dmedian, Dmean, D0.1cc and the V1Gy, V2Gy, V5Gy and V10Gy were analyzed. RESULTS From April 2014 to December 2015, 81 BM were treated with FFF-FSRT/SRS. For the H-H, the average values of Dmedian, Dmean and D0.1cc were 1.5Gy, 1.54Gy and 2.2Gy, respectively, while the V1Gy, V2Gy, V5Gy and V10Gy values were 25%, 8.9%, 8.9% and 2.1%, respectively. For the C-H, the average Dmedian, Dmean and D0.1cc were 0.7Gy, 0.7Gy, 0.9Gy, respectively, while the average values of V1Gy, V2Gy, V5Gy and V10Gy were 18%, 10.2%, 2.8% and 1.4%, respectively. Tumor dimension, tumor cranial-caudal length and the distance between BM and H-H were correlated to Dmedian, Dmean and D0.1cc. For C-H, only the distance from PTV was correlated with a dose reduction. CONCLUSION During FFF-FSRT/SRS, hippocampus received a negligible dose. Despite its clinical significance is still under evaluation, in patients with a long life expectancy, H-H should be considered during Linac-based FSRT/SRS.

Sequential boost in neoadjuvant irradiation for T3N0-1 rectal cancer: long-term results from a single-center experience

Purpose To evaluate the influence of radiation dose on tumor regression grade (TRG) and sphincter preservation rate in a series of cT3N0-1 rectal cancer patients treated with neoadjuvant chemoradiotherapy (CT-RT) with or without a sequential radiation boost. Materials and methods Between May 2002 and September 2013, 116 cases were eligible for retrospective evaluation. Radiotherapy was delivered for a total dose of 45 Gy (no boost arm) or 50.4 Gy (boost arm). TRG was evaluated with the Dworak scale. Results Median follow-up was 62 months (range, 12-138 months). The 5-year overall survival and local control rates were 72% and 93%, respectively. Fifty-five patients (47%) were treated with a sequential radiation boost and 61 (53%) without a boost. Eighty patients (72%) presented T3N0 disease and 32 (28%) T3N1 disease. Concomitant capecitabine was administered in 92 cases (79%) and intravenous 5-fluorouracil in 24 cases (21%). Sphincter preservation was performed in 82% of patients in the boost arm and 66% in the no-boost arm. A higher TRG was related to a longer interval between neoadjuvant treatment and surgery (p<0.001). The probability of a TRG ≥2 was 2.5 times higher in the boost arm. A gain in local control, estimated at 4% during the first 3 years after CT-RT, favored the boost arm. Conclusions The long-term results from our single-center experience confirm literature data on the role of a sequential boost in tumor response after neoadjuvant CT-RT in a series of cT3N0-1 rectal cancer patients.

Increased efficacy of stereotactic ablative radiation therapy after bevacizumab in lung oligometastases from colon cancer

Aim: Metastases from colorectal cancer are poorly responsive to stereotactic ablative radiation therapy (SABR) due to intratumoral hypoxia. Intratumoral oxygenation is improved by administration of angiogenesis inhibitors. Thus, there could be a clinical synergistic effect of SABR with bevacizumab on metastases from colorectal cancer. The aim of this study was to evaluate the feasibility and efficacy of SABR after bevacizumab in lung oligometastases from colon cancer. Methods: The data of patients with lung metastases from colon cancer who underwent SABR were retrospectively evaluated according to the following inclusion criteria: number of metastases ≤3; lung oligometastases from colon cancer in patients who underwent SABR; patients receiving previous chemotherapy alone or in combination with bevacizumab; Karnofsky performance status >80; life expectancy >6 months; at least 6 months’ follow-up after SABR; presence of KRAS mutation. The results were compared with those of a similar cohort of patients with irradiated lung lesions from colorectal cancer in whom bevacizumab was not previously administered. Results: A total of 40 lung metastases were analyzed. The complete response rate after SABR was higher in patients who had received bevacizumab than in those who had not (p = 0.04). Additionally, in the bevacizumab group, a higher rate of post-SABR complete response was observed in case of oligopersistent versus oligorecurrent metastases (p = 0.001). Conclusions: In the setting of lung oligometastases from colon cancer the present study attested the higher efficacy of SABR after bevacizumab administration. Further studies in this field of research are strongly advocated.