Hypofractionated Conformal Radiotherapy Research Articles

Dose outside of the prostate is associated with improved outcomes for high-risk prostate cancer patients treated with brachytherapy boost.

One in three high-risk prostate cancer patients treated with radiotherapy recur. Detection of lymph node metastasis and microscopic disease spread using conventional imaging is poor, and many patients are under-treated due to suboptimal seminal vesicle or lymph node irradiation. We use Image Based Data Mining (IBDM) to investigate association between dose distributions, and prognostic variables and biochemical recurrence (BCR) in prostate cancer patients treated with radiotherapy. We further test whether including dose information in risk-stratification models improves performance. Planning CTs, dose distributions and clinical information were collected for 612 high-risk prostate cancer patients treated with conformal hypo-fractionated radiotherapy, intensity modulated radiotherapy (IMRT), or IMRT plus a single fraction high dose rate (HDR) brachytherapy boost. Dose distributions (including HDR boost) of all studied patients were mapped to a reference anatomy using the prostate delineations. Regions where dose distributions significantly differed between patients that did and did-not experience BCR were assessed voxel-wise using 1) a binary endpoint of BCR at four-years (dose only) and 2) Cox-IBDM (dose and prognostic variables). Regions where dose was associated with outcome were identified. Cox proportional-hazard models with and without region dose information were produced and the Akaike Information Criterion (AIC) was used to assess model performance. No significant regions were observed for patients treated with hypo-fractionated radiotherapy or IMRT. Regions outside the target where higher dose was associated with lower BCR were observed for patients treated with brachytherapy boost. Cox-IBDM revealed that dose response was influenced by age and T-stage. A region at the seminal vesicle tips was identified in binary- and Cox-IBDM. Including the mean dose in this region in a risk-stratification model (hazard ratio=0.84, p=0.005) significantly reduced AIC values (p=0.019), indicating superior performance, compared with prognostic variables only. The region dose was lower in the brachytherapy boost patients compared with the external beam cohorts supporting the occurrence of marginal misses. Association was identified between BCR and dose outside of the target region in high-risk prostate cancer patients treated with IMRT plus brachytherapy boost. We show, for the first-time, that the importance of irradiating this region is linked to prognostic variables.

Conformal hypofractionated radiotherapy for dogs with large adrenal tumours

Adrenalectomy has been recognised as the treatment of choice for adrenal tumours. However, excision of large tumours with or without vena caval tumour thrombi is difficult. The purpose of this...

UNCONVENTIONAL FRACTIONATION RADIOTHERAPY REGIMENS IN TREATMENT OF INOPERABLE LUNG CANCER

The purpose of the study was to compare the efficacy and toxicity of hypofractionated versus hyperfractionated radiotherapy in patients with inoperable lung cancer.Material and Methods. Patients with inoperable lung cancer, who were treated between 2014 and 2017, were assigned to undergo radiotherapy in two arms: accelerated hypofractionated conformal radiotherapy arm with 70 patients (60 Gy in 25 fractions, with 2.4 Gy per fraction) and accelerated hyperfractionated radiotherapy with 49 patients (60–70 Gy with 1–1.5 Gy per fraction). At the same time, platinum-based chemotherapy was applied.Results. The rates of partial response, complete response, stable disease and progressive disease were 44.3, 7.2, 38.5 and 10.0 %, respectively in patients with hypofractionated conformal radiotherapy arm. The corresponding values were 71.4, 6.1, 16.4 and 6.1 %, respectively in patients with hyperfractionated radiotherapy arm. The 2-year overall survival rate was 62.8 % for the hypofractionated group and 58.1 % for the hyperfractionated group. Esophagitis III grade was observed in 4 (5.7 %) patients of the hypofractionated group and in 3 (6.5 %) patients of the hypofractionated group. Pneumonitis III grade was reported in 2 (2.9 %) patients in the hypofractionated radiotherapy arm and in 4 (8.7 %) patients in the hyperfractionated radiotherapy arm.Conclusion. Results of the study showed that 3D-conformal hypofractionated radiotherapy combined with concurrent chemotherapy resulted no in severe radiation-induced complications, and demonstrated satisfactory short-and long-term treatment outcomes.

Prediction of toxicities of prostate cancer radiotherapy.

We treated acohort of 116 patients with prostate cancer with three-dimensional conformal hypofractionated radiotherapy to atotal dose of 52.8 Gy in 16 fractions (3.3 Gy per fraction). The correlation between acute and late gastrointestinal (GI) and genitourinary (GU) toxicity and dose-volume parameters was analysed. Comparison of observed incidence of toxicity and normal tissue complication probability calculated from dose-volume histograms (DVH) of all patients using radiobiological Lyman-Kutcher-Burman model was performed. The results of our study suggest that acute gastrointestinal toxicity ≥ grade 2 (G2) is the significant predictor of late toxicity ≥ G2 (p=0.006). Observed incidence of acute and late GI toxicities ≥ G2 was 9.7% and 11.5%, respectively. NTCPs of acute and late GI complications ≥ G2 were 11.3% and 2.5%. Observed incidence of late GU toxicity ≥ G2 was 14.2%, NTCP was 0.8%. Comparison of calculated probability of acute GI toxicity ≥ G2 and observed incidence indicates that parameters of radiobiological models are set appropriately. Comparison of observed incidence of late GI and GU complications ≥ G2 and calculated NTCPs shows the need of refinement of LKB model parameters for acute and late GI and GU complications ≥ G2. prostate cancer, radiotherapy, acute and late toxicity, radiobiological modeling.

Role of 3D Hypofractionated Radiotherapy in Treatment of High Grade Gliomas: A Prospective Study

Purpose: To evaluate the efficacy and safety of hypofractionated radiotherapy in treatment of patients with high grade glioma. Patients and Methods: A total of thirty patients with high grade glioma referred to clinical oncology and nuclear medicine department, Zagazig University Hospitals between July 2012 to January 2014. All patients were treated with three dimensional (3D) conformal hypofractionated radiotherapy at a dose of 45 Gy/15f treatments over 3 weeks for cases with gross total excision followed by 9Gy in 3 fractions for cases with subtotal excision and biopsy. Results: The median age was 53 years (range 26-66). The median follow up was 12.23 months (range: 4-22 months). One-year overall survival (OAS) and progression free survival (PFS) rates were 58.9% and 12%, respectively. In univariate analysis, age ≥50 years, poor performance status (Karnofasky score of ≥50-70%). Grade IV histology, subtotal excision and overall response to treatment was all associated with statistically significant reduction in OAS and PFS rates. Multivariate analysis, showed that age 70 were the only independent prognostic factors that were associated with good OAS (p= 0.010 and p= 0.015, respectively), and grade III and overall response were the only prognostic factors associated with good PFS (p= 0.002 and p=0.014, respectively). There were minimal side effects to radiation therapy, and all patients complete treatment time without interruption. Conclusion: Conformal hypo fractionated radiotherapy is effective and well tolerated for patients with high grade glioma.

4118 POSTER Prospective Randomized Trial of Hypofractionated Conformal Radiotherapy for Pediatric Diffuse Pontine Glioma

4118 POSTER Prospective Randomized Trial of Hypofractionated Conformal Radiotherapy for Pediatric Diffuse Pontine Glioma

Quality of Life in Men Treated for Early Prostate Cancer: A Prospective Patient Preference Cohort Study

Objectives: In 1997, a study was launched to investigate the treatment of early prostate cancer. Using a patient preference design, health-related quality-of-life (HRQOL) and disease specific HRQOL was assessed prospectively to compare men undergoing radical prostatectomy (RP), hypo-fractionated conformal radiotherapy (CRT) or brachytherapy (BT). Methods: Patients with localised prostate cancer were counselled by a urological surgeon, clinical oncologist and specialist uro-oncology nurse. Patients received treatment according to individual preference. 430 men chose and received RP (n = 217), CRT (n = 161) and BT (n = 52). 354 (82%) completed pre-treatment RAND 36-Item Short-Form Health survey version-2 (SF36v2) and University of California, Los Angeles Prostate cancer index (UCLA-PCI) questionnaires. HRQOL score changes from baseline to 24 months were compared using Kruskall-Wallis test. Results: Pre-treatment, the CRT cohort scored lower for physical function (p = 0.0029) and general health perception (p = 0.0021). The BT cohort reported better baseline scores for urinary function (p = 0.0291), urinary bother (p = 0.0030), sexual function (p = 0.0009) and bowel bother (p = 0.0063). At 24 months, bowel function was similar for CRT and BT but both modalities were worse than RP (p = 0.0010). Urinary continence deteriorated most following RP (p < 0.0001) but BT had worse urinary bother (p = 0.0153). Sexual function deteriorated most following RP and BT (p < 0.0005). Percentages of patients achieving erections adequate for sexual activity (from baseline to 24 months) were 66% to 29% for RP, 62% to 49% for CRT and 88% to 65% for BT. Conclusion: This data demonstrates significant differences in disease specific quality-of-life between RP, CRT and BT and should be available for men with early prostate cancer making treatment decisions.

Dosimetric predictor identification for radiation-induced liver disease after hypofractionated conformal radiotherapy for primary liver carcinoma patients with Child–Pugh Grade A cirrhosis

PurposeRadiation-induced liver disease (RILD) is the most severe complication in liver cancer treatment. The aim of this study was to identify dosimetric predictors for RILD in primary liver carcinoma (PLC) patients with Child–Pugh Grade A cirrhosis after hypofractionated conformal radiotherapy (CRT). Methods and materialsA total of 114 eligible patients (mean age 45years old) were enrolled and treated. The mean gross tumor volume (GTV) was (378.3±308.1) cm3. A median dose of 53Gy was delivered to the PLC by hypofractionated CRT (three fractions/week) with a median fraction size of 4.6Gy (range: 4–6Gy). ResultsPatients were followed up for 1–79months (median 19months) after the completion of irradiation. RILD was diagnosed in nine (7.9%) patients. Univariate analyses revealed that GTV and the percentage of normal liver volume receiving more than 5–40Gy irradiations (V5–40) were related to the risk of developing RILD. Multivariate analyses demonstrated that only GTV and V20 were independent predictors. Using V20 as the predictor for RILD, the accuracy, sensitivity, and specificity was 76.3%, 88.9%, and 75.2%, respectively. ConclusionsOur data suggest that V20 is the unique significant dosimetric predictor for RILD risks in PLC patients with Child–Pugh Grade A cirrhosis after hypofractionated CRT.

Hypofractionated Conformal Radiotherapy (HCRT) for Primary and Metastatic Lung Cancers with Small Dimension

: To report on the clinical outcome of hypofractionated conformal radiotherapy (HCRT) for medically inoperable stage I non-small cell lung carcinoma (NSCLC) or limited pulmonary metastases </= 5 cm in diameter. : From June 2003 to March 2007, 40 patients (42 lesions) underwent HCRT consisting of 40 Gy in five fractions over 2.5 weeks received by at least 95% of planning target volume. All patients underwent CT simulation and treatment under free shallow breathing. To evaluate target displacement under respiratory activity, two additional CT scans were performed with breath-holding during the expiratory and inspiratory phases. Of all patients enrolled, those with a follow-up > or = 4 months were considered suitable for analysis. Local response was evaluated with CT imaging 4 months after the end of HCRT and every 3 months thereafter. Local relapse-free survival (LRFS) and overall survival (OS) were calculated with the Kaplan-Meier method. : Local response to the treatment was complete response, partial response, no change, and progressive disease as seen in 29%, 43%, 14%, and 7% of tumors, respectively. LRFS at 1 year and 3 years was 76% and 63%, respectively. Lung toxicities > or = grade 2 were observed in 4/40 patients, but no grade 4. Pericardial effusion occurred in one patient. In stage I NSCLC patients (n = 15) with a median follow-up of 25 months, the 1-year LRFS and OS rates were 88% and 81%, respectively, and the 3-year rates 72% and 61%, respectively. : HCRT is an effective and low-toxic treatment for medically inoperable early-stage lung cancers and pulmonary metastases for all clinicians lacking the aid of a dedicated stereotactic system.

Phase I study of conformal radiotherapy with concurrent gemcitabine in locally advanced bladder cancer

A prospective phase I trial was conducted to determine the maximal tolerated dose of gemcitabine given once weekly during hypofractionated conformal radiotherapy to patients with locally advanced transitional cell carcinoma of the bladder. Eight male patients, median age 69 years, with Stage T2 (n = 4) or T3 (n = 4) N0M0, were enrolled in cohorts of 3. Treatment comprised conformal radiotherapy (52.5 Gy in 20 fractions) within 4 weeks, with concurrent gemcitabine once weekly for four cycles. The weekly gemcitabine dose was escalated from 100 mg/m(2) in increments of 50 mg/m(2) per cohort. Dose-limiting toxicity was defined as any acute Radiation Therapy Oncology Group (RTOG) toxicity Grade 3 or greater arising in >1 of 3 patients in each cohort. Tumor response was assessed cystoscopically and radiologically at 3 months. All 8 patients completed radiotherapy, and 6 of 8 completed chemoradiotherapy. No acute toxicity greater than RTOG Grade 1 was seen with gemcitabine at 100 mg/m(2). Dose-limiting toxicity was observed at 150 mg/m(2) with Grade 3 toxicity seen in 2 of 2 patients (one bladder, one bowel). An additional 3 patients received 100 mg/m(2) with minimal toxicity. No hematologic toxicity was encountered. A complete response was seen in 7 (87.5%) of 8 patients, all of whom were disease free at a median follow-up of 19.5 months (range, 14-23 months). No late toxicity (greater than RTOG Grade 0) has been observed. The maximal tolerated dose for gemcitabine given once weekly with concurrent hypofractionated conformal bladder radiotherapy was 150 mg/m(2), with a maximal recommended dose of 100 mg/m(2). This dose regimen has now entered Phase II clinical trials.

786 poster A dosimetric feasibility study of Conformal Radiotherapy (CRT) vs. Hypofractionated CRT (HCRT) vs. Intensity Modulated Radiotherapy (IMRT) vs. Simultaneously Integrated Hypofractionated Boost IMRT (SIHB) in prostate adenocarcinoma

786 poster A dosimetric feasibility study of Conformal Radiotherapy (CRT) vs. Hypofractionated CRT (HCRT) vs. Intensity Modulated Radiotherapy (IMRT) vs. Simultaneously Integrated Hypofractionated Boost IMRT (SIHB) in prostate adenocarcinoma

Prone accelerated partial breast irradiation (five fractions) after breast conservation therapy with heart and lung sparing

870 Background: The convenience of a shorter course of adjuvant radiation after breast conservation therapy (BCT) has encouraged the exploration of partial breast radiation techniques. We are reporting the clinical and physical results of the first 47 patients accrued to an ongoing accelerated partial breast irradiation (APBI) protocol utilizing three dimensional conformal radiation therapy (3D-CRT) in prone position after BCT ( supported by DOD DAMD 17–01-1–0345). Methods: A regimen of external beam conformal hypo-fractionated radiotherapy directed to the original tumor bed with margins was prospectively tested in a phase I/II study. Post-menopausal women with non-palpable T1N0 breast cancer, excised with at least 5 mm margins, lack of EIC, and receptor positive tumors were offered eligibility to the study only if they had first refused six weeks of standard radiation. Planning CT and treatment were performed in the prone position, on a dedicated table to best spare heart and lung tissues. The planning target volume (PTV) was defined at CT as the post-excisoinal surgical cavity plus a 2 cm margin(Varian Somavision/CadPlan/Eclipse). Based on radiobiological modeling, the prescribed dose (PD) was 6 Gy per fraction delivered to the 95% isodose surface in 5 fractions over ten days to a total dose of 30 Gy. A 2-stage Simon design with projected enrollment of at most 99 patients was used (significance level of 0.05 and power of 0.80). Results: 47 patients have completed treatment. Median age is 67.5 years (51 –85) and median tumor diameter is 1 cm (0.2–1.9). Acute effects were limited to Grade 1–2 erythema in 22/47 patients (47%). The mean volume of the ipsilateral breast (IBV) receiving 100% of the PD was 26% (range 10–45%). The mean volume receiving 50% of the PD was 47% (range 23–75%). In all patients no significant heart or lung volume was treated by the prone technique. At a median follow-up of 2 years, no patient has recurred. Conclusions: These preliminary data support the feasibility of prone APBI, which is well tolerated and enables heart and lung sparing. Longer follow-up is required to assess efficacy and long term cosmetic results. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Department of Defense DAMD17–01-1–0345; 2001–2004 P.I.Formenti, S.C.

899 Poster Hypofractionated conformal radiotherapy with neoadjuvant and concommitant hormonal therapy in the treatment of intermediate risk prostate cancer: report on acute toxicity

899 Poster Hypofractionated conformal radiotherapy with neoadjuvant and concommitant hormonal therapy in the treatment of intermediate risk prostate cancer: report on acute toxicity