Quantitative CT texture analysis in predicting PD-L1 expression in locally advanced or metastatic NSCLC patients.

PURPOSE: The assessment of Programmed death-ligand 1 (PD-L1) expression has become a game changer in the treatment of patients with advanced non-small cell lung cancer (NSCLC). We aimed to investigate the ability of Radiomics applied to computed tomography (CT) in predicting PD-L1 expression in patients with advanced NSCLC. METHODS: By applying texture analysis, we retrospectively analyzed 72 patients with advanced NSCLC. The datasets were randomly split into a training cohort (2/3) and a validation cohort (1/3). Forty radiomic features were extracted by manually drawing tumor volumes of interest (VOIs) on baseline contrast-enhanced CT. After selecting features on the training cohort, two predictive models were created using binary logistic regression, one for PD-L1 values ≥ 50% and the other for values between 1 and 49%. The two models were analyzed with ROC curves and tested in the validation cohort. RESULTS: The Radiomic Score (Rad-Score) for PD-L1 values ≥ 50%, which consisted of Skewness and Low Gray-Level Zone Emphasis (GLZLM_LGZE), presented a cut-off value of - 0.745 with an area under the curve (AUC) of 0.811 and 0.789 in the training and validation cohort, respectively. The Rad-Score for PD-L1 values between 1 and 49% consisted of Sphericity, Skewness, Conv_Q3 and Gray Level Non-Uniformity (GLZLM_GLNU), showing a cut-off value of 0.111 with AUC of 0.763 and 0.806 in the two population, respectively. CONCLUSION: Rad-Scores obtained from CT texture analysis could be useful for predicting PD-L1 expression and guiding the therapeutic choice in patients with advanced NSCLC.

Treatment of grade II-III intracranial meningioma with helical tomotherapy.

Meningiomas account for 30-35% of intracranial tumors. Grade I meningiomas are most common and carry the best prognosis. Grade II and III meningiomas are more aggressive and the outcomes after surgical resection alone remain unsatisfactory. The main objective of this retrospective, single-center study was to assess our results of treatment of grade II-III intracranial meningioma with helical tomotherapy (HT). We retrospectively reviewed patients with histologically proven (WHO 2007) grade II-III meningioma irradiated with HT. Patients were treated one session a day, 5 days a week, to a total dose of 59.4 Gy and 68.4 Gy delivered in 33 and 38 fractions of 1.8 Gy each to the LR PTV and HR PTV, with or without simultaneous integrated boost. From May 2011 to January 2015, 19 patients (15 with grade II and 4 with grade III meningiomas) were treated. Median follow-up for patients with Grade II or Grade III meningiomas, was 29.2 months (range, 10.7-52.4) and 21.3 months (range, 2.4-51.3), respectively. Disease free survival at 1, 2 and 3 years was 89.2%, 83.6% and 56.3% respectively. Overall survival at 1, 2 and 3 years was 94.7%, 94.7% and 78.9%, respectively. No patient had neurological toxicity greater than grade 2 in the acute period. During follow-up, only one patient had neurological toxicity greater than or equal to grade 3. The management of grade II to III meningiomas using HT with doses exceeding 60 Gy is associated with good local control and acceptable survival results.

Postoperative Hypofractionated Radiotherapy for Prostate Cancer.

AIM: To retrospectively investigate outcomes, and acute and late complications following postoperative hypofractionated 3D conformal radiotherapy. PATIENTS AND METHODS: Sixty-nine consecutive patients underwent radical prostatectomy. Radiotherapy was delivered to the prostatic fossa by means of a7-fieldLINACwith 6-15 MV to a total dose of 62.5 Gy in 25 fractions (2.5 Gy per fraction) in five consecutive weeks. RESULTS: Median follow-up was 54.7 months (range=38-76 months). Five-year overall survival, metastasis-free survival and biochemical relapse-free survival were 91.1%, 84.6% and 66.7%, respectively. Grade 2 or more genitourinary and gastrointestinal acute toxicity was reported in 12% and 5% of patients, respectively. Urinary incontinence grade 2 or more was recorded in 19%. CONCLUSION: Postoperative radiotherapy either in the adjuvant or salvage setting resulted in acceptable rates of acute and late toxicity with good tumor control while reducing overall treatment time. Confirmatory results from an ongoing prospective trial are awaited.

Treatment outcomes and patterns of radiologic appearance after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) for lung tumours.

OBJECTIVE: To evaluate treatment outcomes and patterns of CT lung injury after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) in a series of inoperable lung lesions. METHODS: 68 patients who were medically inoperable (69 lesions) without evidence of viable extrathoracic disease were included. Dose prescription was driven by tumour location (hilar/pericentral vs peripheral) and/or target volume. 52% of the lesions received a biological equivalent dose (BED10) ≥100 Gy. Assessment of tumour response was based on the Response Evaluation Criteria in Solid Tumours 1.1 criteria coupled with fluorine-18 fludeoxyglucose/positron emission tomography-CT. Toxicity monitoring was focused on treatment-related pulmonary adverse events according to the Common Terminology Criteria for Adverse Events v. 4.0. Acute and late events were classified as radiation pneumonitis (RP) and radiation fibrosis (RF), respectively. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate analyses of survival were performed using the Cox proportional hazards model. RESULTS: After a median follow-up of 12 months (range, 3-31 months), no instances of ≥Grade 4 RP was documented, and clinically severe (Grade 3) RP occurred in 5.8% of the patients. 2 (3%) patients developed a late severe (≥Grade 3) symptomatic RF. No specific pattern of CT lung injury was demonstrated, in both acute and late settings. Median overall survival (OS) and progression-free survival (PFS) for the entire population were 30.8 and 14.1 months, respectively. At multivariate analysis (MVA), BED10 ≥ 100 Gy and KPS ≥ 90 emerged as significant prognostic factors for OS (p = 0.01 and p = 0.001, respectively), and BED10 ≥ 100 Gy for PFS (p = 0.02). CONCLUSION: Our findings show that HHT adjusted for tumour location and/or target volume is an effective treatment with an acceptable toxicity profile in patients who are medically inoperable with lung tumours and is not associated with a specific pattern of lung injury. Therefore, it can represent a viable option when conventional stereotactic ablative radiotherapy facilities are not available. Advances in knowledge: The present study is among the largest series addressing the role of HHT for inoperable lung tumours. This technique is safe and effective and is not associated with a specific pattern of lung injury, at least at early and average time points.

Second cancer incidence in primary mediastinal B-cell lymphoma treated with methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin regimen with or without rituximab and mediastinal radiotherapy: Results from a monoinstitutional cohort analysis of long-term survivors.

Our aim is to assess the incidence of second cancer in long-time surviving primary mediastinal B-cell lymphoma (PMBCL) patients treated with combined radiochemoimmunotherapy (standard methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin with rituximab and mediastinal radiation therapy at a dose of 30 to 36 Gy). For this purpose, 92 points were evaluated. After a median overall survival of 137 months (range 76-212), we recorded second cancer in 3 of 80 long-surviving patients (3.75%) with cumulative incidence of 3.47% at 15 years and 11% at 17 years, with a 17-year second cancer-free survival of 82%. We observed 2 papillary thyroid cancers with a standardized incidence ratio (SIR) of 7.97 and an absolute excess risk (AER) of 17. 84 and 1 acute myeloid leukemia (AML) with an SIR of 66.53 and an AER of 10.05. No breast cancer occurred. Although we should take into account the limits of the proposed statistical analysis, combined modality treatment was related to a significant SIR and AER for thyroid cancer and acute myeloid leukemia.

Potential Role of Single Nucleotide Polymorphisms of XRCC1, XRCC3, and RAD51 in Predicting Acute Toxicity in Rectal Cancer Patients Treated With Preoperative Radiochemotherapy.

OBJECTIVES: To investigate the association between polymorphisms of DNA repair genes and xenobiotic with acute adverse effects in locally advanced rectal cancer patients treated with neoadjuvant radiochemotherapy. METHODS: Sixty-seven patients were analyzed for the current study. Genotypes in DNA repair genes XRCC1 (G28152A), XRCC3 (A4541G), XRCC3 (C18067T), RAD51 (G315C), and GSTP1 (A313G) were determined by pyrosequencing technology. RESULTS: The observed grade ≥3 acute toxicity rates were 23.8%. Chemotherapy and radiotherapy were interrupted for 46 and 14 days, respectively, due to critical complications. Four patients were hospitalized, 6 patients had been admitted to the ER, and 5 patients received invasive procedures (2 bladder catheters, 2 blood transfusions, and 1 growth factor therapy).RAD51 correlated with acute severe gastrointestinal toxicity in heterozygosity (Aa) and homozygosity (AA) (P=0.036). Grade ≥3 abdominal/pelvis pain toxicity was higher in the Aa group (P=0.017) and in the Aa+AA group (P=0.027) compared with homozygous (aa) patients. Acute skin toxicity of any grade occurred in 55.6% of the mutated patients versus 22.8% in the wild-type group (P=0.04) for RAD51. XRCC1 correlated with skin toxicity of any grade in the Aa+AA group (P=0.03) and in the Aa group alone (P=0.044). Grade ≥3 urinary frequency/urgency was significantly higher in patients with AA (P=0.01), Aa (P=0.022), and Aa+AA (P=0.031) for XRCC3 compared with aa group. CONCLUSIONS: Our study suggested that RAD51, XRCC1, and XRCC3 polymorphisms may be predictive factors for radiation-induced acute toxicity in rectal cancer patients treated with preoperative combined therapy.

Lung Metastases Treated With Stereotactic Ablative Radiation Therapy in Oligometastatic Colorectal Cancer Patients: Outcomes and Prognostic Factors After Long-Term Follow-Up.

BACKGROUND: We evaluated a series of oligometastatic colorectal cancer (CRC) patients treated with stereotactic ablative body radiotherapy (SABR) delivered in all active lung metastases. PATIENTS AND METHODS: Forty-four patients with 69 lung metastases were treated with SABR. Eleven patients presented with other sites of metastases before stereotactic body radiotherapy (SBRT), even though they had controlled/cured systemic disease. RESULTS: The median follow-up was 36 months. The median overall survival (OS) was 38 months and 2 years, 3-year OS rates were 67.7% and 50.8%, respectively. The median progression-free survival (PFS) was 10 months and 2 years, 3-year PFS rates were 20.3% and 16.2%, respectively. Local recurrence occurred in 16 patients (36%).The first site of failure was local only in 22%, distant only in 35%, and local and distant in 14% of the patients. The 1-year, 2-year, and 3-year local PFS (LPFS) were 68.8%, 60.2%, and 54.2%, respectively. No Grade ≥ 3 toxicities were recorded in the univariate analysis; multiple lung metastases and synchronous oligometastatic disease were significantly associated with worse PFS (P = .04, and P < .001, respectively) and worse metastases-free survival (MFS; P = .04, and P < .001, respectively). The type of response was identified as a significant prognostic factor for OS (P = .014), PFS (P = .006), and LPFS (P < .001). In multivariate analysis single lung metastases treated with SBRT was associated with better MFS (P = .015). Metachronous oligometastatic disease and type of response were associated with significantly better PFS. CONCLUSION: Stereotactic body radiotherapy is a valid therapy in the treatment of lung metastases for oligometastatic CRC patients presenting long survival. The rate of local control remains lower compared with other primaries. Further prospective cohorts would better evaluate effective fractionation for patients with oligometastatic CRC.

Role of irradiation for patients over 80 years old with glioblastoma: a retrospective cohort study.

To assess efficacy and safety of hypofractionated radiation therapy (HRT) in patients over 80 years old with newly diagnosed glioblastoma (GBM). Between June 2009 and September 2015, patients in this population with a recommendation for radiation therapy from a multidisciplinary tumor board, and a Karnofsky performance status (KPS) ≥60 as assessed by a radiation oncologist, who received HRT (40 Gy/15 fractions) ± concomitant and adjuvant temozolomide (TMZ) were retrospectively analyzed. A total of 21 patients fulfilled the criteria for eligibility. Median KPS was 80 (60-90). After a median follow-up of 5.8 months (IQR 3.7-13.1 months), median overall survival (OS) was 7.5 months (95 % CI 4.5-19.1) and the 1-year and 2-year OS were 39.5 % (95 % CI 21.9-71.2 %) and 6.6 % (95 % CI 1.0- 43.3 %), respectively. Median progression-free survival (PFS) was 5.8 months (95 % CI 3.9-7.7 months), 1-year and 2-year PFS were 15.2 % (95 % CI 4.4-52.4) and 0 %, respectively. Overall, 16 (76.2 %) patients presented a recurrence. Overall seven patients (33.3 %) needed to be hospitalized during treatment. On univariate analysis, hospitalization was the only variable that correlated with less favourable outcome in terms of both OS (12.2 months versus 3.8 months, p < 0.010) and PFS (5.8 months versus 3.4 months, p = 0.002). Our study suggests that HRT is feasible with acceptable tolerance among "very elderly" patients affected by GBM. Patients 80 and older should be considered for management based on RT.

Different outcomes among favourable and unfavourable intermediate-risk prostate cancer patients treated with hypofractionated radiotherapy and androgen deprivation therapy.

BACKGROUND: to evaluate the role of a risk stratification system in intermediate-risk prostate cancer (PCa) treated with hypofractionated radiotherapy (HyRT). METHODS: 131 patients affected by intermediate-risk PCa were treated with HyRT at the total dose of 54,75 Gy in 15 fraction plus 9 months of androgen deprivation therapy (ADT). Patients were classified as favourable risk (FIR) if they had a single NCCN intermediate-risk factor (IRF), a Gleason score ≤3 + 4 = 7, and <50 % of biopsy cores containing cancer (PBCC). If these criteria were not met were classified as unfavourable risk (UIR). Univariate and multivariate analyses using Cox proportional hazards model were calculated for biochemical recurrence-free survival (bRFS), the risk of local recurrence and metastasis-free survival (MFS). RESULTS: After a median follow-up of 56.7 months (range 9.8 to 93.7 months), 11 patients (8.4 %) died, of whom 2 (1.5 %) for PCa. In the univariate analysis, Gleason score, PPBCs, IRFs and PSA at first follow-up were prognostic factors for bRFS and LF while Gleason score, PPBCs and PSA at first follow-up were significant predictor for MFS. In the multivariate analysis only the PSA at first follow-up resulted a prognostic factor for bRFS and MFS. Patients with a value of PSA at first follow-up <0.7 ng/mL respect to those with PSA ≥0,7 ng/mL had a 5y-bRFS of 93.3 % vs. 57.5 %, 5y-MFS of 99.0 % vs. 78.9 % and 5y-LF of 5.8 % vs. 38.3 %. Patients in the UIR PCa group with a PSA value <0.7 ng/mL at first follow-up had significant better bRFS, LF and MFS. CONCLUSIONS: Risk factors currently not included in the guidelines are useful to stratify patients with intermediate-risk PCa in two groups of different prognosis even when HyRT is delivered. PSA at first follow-up is useful in UIR PCa to guide the overall length of ADT.

Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study.

PURPOSE: Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS). METHODS AND MATERIALS: From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE]; range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively. RESULTS: With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5- and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age <40 years and primary disease status were independent favorable prognostic factors for progression-free survival and OS, and local tumor control was an independent favorable predictor of OS. In contrast, the extent of surgery, dosimetric parameters, and adjacent organs at risk were not prognostic factors for LC or OS. CONCLUSIONS: Systematic high-dose postoperative proton therapy for skull base chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended.

Renin-Angiotensin System Inhibitors Might Help to Reduce the Development of Symptomatic Radiation Pneumonitis After Stereotactic Body Radiotherapy for Lung Cancer.

INTRODUCTION: The purpose of the present study was to evaluate the role of renin-angiotensin system (RAS) inhibitors in preventing symptomatic radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: The data from 158 patients with a solitary lung lesion treated with 1 to 3 fractions of SBRT from December 2008 to July 2014 were retrospectively analyzed. The incidence of RP was evaluated according to the Common Toxicity Criteria for Adverse Events, version 4. The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) was analyzed to assess for possible correlations with the development of grade ≥ 2 RP. The patient and dosimetric variables were also assessed. RESULTS: After a median follow-up period of 13.8 months (range, 3.2-55.0 months), 22 patients had developed grade ≥ 2 RP. Patients with peripheral lesions, favorable dosimetric data, and ACEI and/or ARB use had a reduced risk of symptomatic RP. In unadjusted and adjusted multivariate analyses, ACEI and/or ARB intake and the dosimetric variables were statistically significant factors. In a secondary analysis, the use of ACEIs and ARBs among patients with a greater planning target volume and higher dosimetric values correlated with a reduced risk of symptomatic RP. CONCLUSION: The use of a RAS inhibitor was associated with a decreased incidence of symptomatic RP among patients undergoing SBRT for lung lesions. Patients with higher dosimetric values had a reduced risk of grade ≥ 2 RP with ACEI and ARB use.

Stereotactic Ablative Body Radiotherapy (SABR) in Pulmonary Oligometastatic/Oligorecurrent Non-small Cell Lung Cancer Patients: A New Therapeutic Approach.

AIM: Stage IV non-small cell lung cancer (NSCLC) is characterized by poor prognosis. Palliative chemotherapy and/or best supportive care are considered standard treatment. Nevertheless, for patients with limited distant metastases (1-5 metastases), called oligometastatic disease, better prognosis has been observed. We evaluated response rate, survival, time to progression and toxicity in oligometastatic/oligorecurrent NSCLC patients treated with stereotactic body radiotherapy (SBRT) delivered to all active sites in the lung. PATIENTS AND METHODS: Twenty-nine lung metastases in 22 patients affected by oligometastatic/oligorecurrent NSCLC were treated with SBRT to all active sites of disease. Inclusion criteria were: controlled primary tumor with complete response or stable disease after surgery/radiotherapy/combined therapy; ≤4 synchronous or metachronous lung metastases at the time of treatment; no other active sites of distant metastases. RESULTS: Response to treatment was as follows: complete response in 21% of lesions, partial response in 69% of metastases, stable disease in 10%. Ninenty-one percent of patients had complete metabolic response, and 9% had a partial metabolic response. Median follow-up was 18 months. The 1-year and 2-year OS was 86% and 49%, respectively. The 1-year and 2-year PFS was 79% and 40%, respectively. Median time to progression and median OS were 18 months and 24 months, respectively. Local control was 93% at 1 year and 64% at 2 years. Overall, acute toxicity occurred in 18% (4/22) of patients; two patients experienced grade 2 pneumonitis. Grade ≤2 late toxicity occurred in 50% of patients. No grade ≥3 toxicities were recorded. CONCLUSION: Aggressive stereotactic radiotherapy is a feasible and well-tolerated treatment for oligometastatic/oligorrecurrent NSCLC patients with lung metastases offering longer survival. Ablative radio therapy has a potential role in the management of well-selected stage IV NSCLC patients while increasing their quality of life and survival.

Hypofractionated Image-guided Radiation Therapy (3Gy/fraction) in Patients Affected by Inoperable Advanced-stage Non-small Cell Lung Cancer After Long-term Follow-up.

BACKGROUND: We conducted long-term follow-up analysis of the outcomes for patients affected by advanced-stage non-small cell lung cancer (NSCLC) treated with hypofractionated radiotherapy (RT). MATERIALS AND METHODS: Sixty patients with advanced-stage NSCLC (IIIA-IV) treated with hypofractionated radiotherapy (60Gy/20 fractions) were analyzed. Radiation was delivered using an image-guided RT technique to verify the correct position. Toxicities were graded according to the Common Toxicity Criteria for Adverse Effects v4.0 scale. RESULTS: Overall, six patients achieved a complete response and 46 patients had a partial response (tumor response rate 86%). After a median follow-up of 30 months, locoregional progression occurred in 23 patients and distant progression occurred in 38. The 1-year and 2-years overall survival were 57% and 40%, respectively. The 1-year and 2-years progression-free survival (PFS) were 47.1% and 33.5%, respectively. The median duration of OS and PFS was 13 months and 12 months, respectively. The 2-year local PFS and metastases-free survival (MFS) were 53% and 40.3%, respectively. On univariate analysis, the T-size (≥5 cm), and type of response to RT (non-response/progressive disease) were significantly associated with worse OS. Type of response was identified as significant prognostic factors for PFS (p<0.01) local PFS (p=0.015) and MFS (p<0.01). Acute grade 3 esophagitis and pneumonitis occurred in three patients (5%) and four patients (6%), respectively. Late grade 3 esophagitis and pneumonitis occurred in 2% (one patient) and 3% (two patients), respectively. No patient experienced grade 4 acute or late RT-related toxicities. CONCLUSION: Hypofractionated RT offers good disease control for patients with advanced-stage NSCLC with acceptable toxicity rates. Phase III randomized trials are necessary to compare hypofractionated RT with conventional RT.

Stereotactic Body Radiation Therapy for Liver Lesions. A Single-institution Experience.

AIM: To evaluate survival and toxicity in a cohort of patients treated with stereotactic body radiation therapy (SBRT) for unresectable intrahepatic malignancies. PATIENTS AND METHODS: From 2007 to 2014, 23 patients with 34 lesions (three primary and 31 metastatic liver tumors) were treated with SBRT. RESULTS: The median follow-up was 9 months (range=1-76) for all patients. Local control was reached in 27 out of 34 (79%) treated lesions, with 1 and 2 years rates of 93% and 73%, respectively. The progression-free survival at 1-year and 2-year was 50% and 25%, respectively. Median overall survival was 16 months (95% confidence interval=8-24 months), with 1-year and 2-year rates of 58% and 41%, respectively. Toxicity was very low consisting mainly of grade 1 and 2 events. CONCLUSION: SBRT provides good local control for both primary and metastatic liver lesions, with minimal toxicity.

Multifraction radiotherapy for palliation of painful bone metastases: 20 Gy versus 30 Gy.

AIMS AND BACKGROUND: To compare 2 multifraction radiotherapy schedules in the palliation of painful bone metastases. METHODS AND STUDY DESIGN: We retrospectively analyzed clinical data of 105 patients with a total of 140 painful bone metastases who were treated with 20 Gy in 5 fractions or 30 Gy in 10 fractions. The primary tumors were breast (30%), lung (28%), and prostate (14%). The main sites of irradiation were spine (n = 79) and sacrum or pelvis (n = 39). Pain was graded by patients according to the pain numeric rating scale just before and 1 month after radiotherapy. Pain progression was defined as an increase ≥2 on pain scale after an initial response. RESULTS: The overall response rate at 1 month was 88.6%. Overall response rate was 89.6% in the 20-Gy arm and 87.3% in the 30-Gy arm (p = 0.669). The rate of complete response was statistically better in patients treated with 30 Gy (p = 0.019). The mean reduction in pain was 3.2 in the 20-Gy group and 3.6 in the 30-Gy group. Pain progression was 6.5% and 1.6%, respectively. The incidence of acute toxicity was statistically significantly higher in the 30-Gy arm (23.8%) than in the 20-Gy arm (2.6%) (p = 0.001). One pathologic fracture of the irradiated bone was observed in the 30-Gy arm. Two lesions, one in each group, were re-irradiated for pain recurrence. Pain progression was found in 6.5% of the irradiated lesions in the 20-Gy arm and in 1.6% in the 30-Gy arm. CONCLUSIONS: In our series, both regimens achieved high rate of pain relief, although the group treated with higher total dose reported better complete response rate. The 30-Gy arm had a significantly higher rate of acute toxicity.

Role of salvage stereotactic body radiation therapy in post-surgical loco-regional recurrence in a selected population of non-small cell lung cancer patients.

AIM: This is a retrospective analysis of a selected series of high-risk non-small cell lung cancer (NSCLC) patients with post-surgical loco-regional relapse treated with salvage stereotactic body radiotherapy (SBRT). Outcome and toxicity profiles were assessed. PATIENTS AND METHODS: Twenty-eight patients (unfit for surgery or systemic therapy) with 30 lesions underwent salvage SBRT as an alternative therapy because of advanced age, co-morbid conditions or no response obtained from other treatments. RESULTS: Complete and partial responses were 16% and 70%, respectively. Local progression was observed in 3 patients. Regional relapse occurred in 5 patients. Distant progression occurred in 10 patients. The 2-year overall survival (OS) and disease-free survival (DFS) were 57.5% and 36.6%, respectively. Radiation acute pneumonitis occurred as follows: three patients developed grade 1, two patients experienced grade 2 and one patient experienced grade 3 toxicity. CONCLUSION: Stereotactic body radiotherapy could have an alternative role in isolated loco-regional relapse in patients unfit or resistant to other therapies.

Manipulation of radiation-induced bystander effect in prostate adenocarcinoma by dose and tumor differentiation grade: in vitro study.

PURPOSE: This in vitro study evaluated the ability of prostate adenocarcinoma (ADC) cells to induce radiation-induced bystander effect (RIBE) exploring the factors that may be responsible and affect its intensity. The idea was to mimic a strong, clinically applicable RIBE that could lead to the development of innovative approaches in modern radiotherapy of prostate cancer, especially for those patients with hormone-refractory ADC in which radiotherapy might have a limited role. MATERIALS AND METHODS: Two human prostate cancer cell lines of different differentiation, PC-3 and DU-145, have been irradiated using wide range of doses to obtain radiation-conditioned medium (RCM), which was used to treat the unirradiated cells and to evaluate the cytokines level. Using a trypan blue dye exclusion method, cell growth was assessed. RESULTS: Prostate ADC cells were able to induce RIBE; intensity depended on dose and cell differentiation. RIBE intensity of DU-145 was not correlated with the cytokines level, while for PC-3 Interleukin-6 (IL-6) correlates with strongest RIBE induced by 20 Gy. CONCLUSIONS: RIBE can be manipulated by modifying radiation dose and depends on cell differentiation status. IL-6 correlates with RIBE after exposure of PC-3 to a very high dose of radiation, thus indicates its possible involvement in bystander signaling.

Neoadjuvant chemoradiation with concomitant boost radiotherapy associated to capecitabine in rectal cancer patients.

PURPOSE: The primary end-points were complete pathological response and local control. Secondary end-points were survivals, anal sphincter preservation, and toxicity profile. METHODS: Patients with T3/T4 and or N+ rectal cancer (n = 65) were treated with preoperative concomitant boost radiotherapy (55 Gy/25 fractions) associated to concurrent chemotherapy with oral capecitabine. RESULTS: All patients completed the programmed treatment. The complete pathological response was achieved by 17 % of the patients. Anal sphincter preservation surgery was possible for 86 % of the patients with low rectal cancer (≤ 5 cm from the anal verge). The T-stage and N-stage downstaging were achieved by 40 and 58 % of the patients, respectively. Circumferential radial margin was involved (close/positive) in eight patients. After a median follow-up of 26 months, local and distant recurrence occurred in two and 11 patients, respectively. The 3-year overall survival and disease-free survival were 86.8 and 81 %, respectively. Non-hematological ≥ grade 3 toxicities were observed in 15 % of the patients. On univariate analysis N-downstaging and positive circumferential radial margin were significantly associated with worse overall survival (p = 0.003 and p = 0.023, respectively), disease-free survival (p = 0.001 and p = 0.036, respectively), and metastasis-free survival (MFS) (p = 0.001 and p = 0.038, respectively).On multivariate analysis, the N-downstaging were significantly associated with better overall survival (OS) (p = 0.022). CONCLUSIONS: Our data support the efficacy of preoperative treatment for rectal cancer in terms of local outcomes. Radiation treatment intensification may have a biological rationale; longer follow-up is needed.

Hypofractionated intensity-modulated simultaneous integrated boost and image-guided radiotherapy in the treatment of high-risk prostate cancer patients: a preliminary report on acute toxicity.

AIMS AND BACKGROUND: To evaluate acute toxicity of hypofractionated intensity-modulated radiotherapy with simultaneous integrated boost and image-guided radiotherapy in the treatment of high-risk prostate cancer patients. METHODS: Between November 2009 and March 2012, 59 patients with high-risk prostate cancer were enrolled. The eclipse inverse planning system (Varian) was used to calculate an IMRT plan with simultaneous integrated boost, delivering 68.75 Gy (2.75 Gy per fraction) to the prostate, 55 Gy (2.2 Gy per fraction) to the seminal vesicles and positive nodes, and 45 Gy (1.8 Gy per fraction) to the pelvis, 4 fractions per week, 25 fractions. Prior to each treatment, patients underwent a kilo-voltage cone-beam CT performing an image-guided radiation therapy (IGRT). All patients were submitted to neoadjuvant, concomitant and adjuvant hormone therapy. RESULTS: The median follow-up for all patients was 13 months (range, 3-28). At the last follow-up, no grade 3 or 4 side effect was observed. Toxicity occurred as follows during the treatment: grade 1 and 2 gastrointestinal toxicity 5.2% and 6.9%, respectively; grade 1 and 2 genitourinary toxicity 24.1% and 1.7%, respectively. Only 1.7% of the patients developed grade 3 genitourinary toxicity. No grade 3 gastrointestinal toxicity was observed. CONCLUSIONS: The present study demonstrated that 4/w hypofractionated intensity-modulated radiotherapy with simultaneous integrated boost and image-guided radiotherapy in patients with high-risk prostate cancer is feasible and safe. Low acute toxicity rates were verified. Longer follow-up is needed to evaluate the outcomes in terms of late toxicity and survival.

Intermediate-risk prostate cancer patients treated with androgen deprivation therapy and a hypofractionated radiation regimen with or without image guided radiotherapy.

BACKGROUND: To evaluate the efficacy of hypofractionated radiotherapy (HyRT) with or without image guided radiotherapy (IGRT) in intermediate risk prostate cancer. METHODS: 105 patients were treated with HyRT, 43,8 Gy and 54,75 Gy were delivered to the seminal vescicles and to the prostate, respectively; 3,65 Gy/fraction three times weekly. All patients underwent 9 months hormonal therapy. Patient position was verified with daily kV cone beam CT in 69 patients (IGRT group). Acute and late toxicities were evaluated according to RTOG scale. Biochemical relapse was defined using PSA nadir + 2 ng/mL. The data were prospectively collected and retrospectively analyzed to evaluate the efficacy of IGRT. RESULTS: After a median follow-up of 31 months the actuarial 3-year bNED was 93,7%. During RT, 10.5% and 7.6% of patients developed ≥Grade 2 rectal and urinary toxicities, respectively. The cumulative incidence of ≥Grade 2 late rectal and urinary toxicities at 3 years were 6,9%, and 10,8%, respectively. The incidence of ≥Grade 2 late rectal toxicities was significant reduced in the IGRT group (1,6% vs. 14,5%, p=0,021). Two patients developed Grade 3 urethral obstruction and one patient developed grade 3 rectal bleeding. CONCLUSIONS: HyRT represents a well-tolerated treatment able to achieve a high bNED. The use of daily IGRT is beneficial for reducing the incidence of late toxicities.