Post-Operative Radiotherapy in Prostate Cancer: Is It Time for a Belt and Braces Approach?

Approximately 30% of patients treated with radical prostatectomy (RP) for prostate cancers experience biochemical recurrence (BCR). Post-operative radiation therapy (RT) can be either offered immediately after the surgery in case of aggressive pathological features or proposed early if BCR occurs. Until recently, little data were available regarding the optimal RT timing, protocol, volumes to treat, and the benefit of adding androgen deprivation therapies to post-operative RT. In this review, we aim to pragmatically discuss current literature data on these points. Early salvage RT appears to be the optimal post-operative approach, improving oncological outcomes especially with low prostate-specific antigen (PSA) levels, as well as sparing several unnecessary adjuvant treatments. The standard RT dose is still 64–66 Gy to the prostate bed in conventional fractionation, but hypofractionation protocols are emerging pending on late toxicity data. Several scientific societies have published contouring atlases, even though they are heterogeneous and deserve future consensus. During salvage RT, the inclusion of pelvic lymph nodes is also controversial, but preliminary data show a possible benefit for PSA > 0.34 ng/ml at the cost of increased hematological side effects. Concomitant ADT and its duration are also discussed, possibly advantageous (at least in terms of metastasis-free survival) for PSA rates over 0.6 ng/ml, taking into account life expectancy and cardiovascular comorbidities. Intensified regimens, for instance, with new-generation hormone therapies, could further improve outcomes in carefully selected patients. Finally, recent advances in molecular imaging, as well as upcoming breakthroughs in genomics and artificial intelligence tools, could soon reshuffle the cards of the current therapeutic strategy.

RADT-11. INCREASED USE OF HYPOFRACTIONATED RADIOTHERAPY IN ELDERLY PATIENTS WITH GLIOBLASTOMA IN THE UNITED STATES FROM 2004-2015

PURPOSE/OBJECTIVES The prognosis for glioblastoma in elderly patients is poor; randomized trials have demonstrated comparable survival following adjuvant radiotherapy (RT) using conventional or hypofractionation. We used the National Cancer Database (NCDB) to measure trends in the use of hypofractionated RT in glioblastoma patients 70 years of age and older. MATERIALS AND METHODS The NCDB was queried for elderly glioblastoma patients treated with a known RT dosing schema from 2004-2015 (n=10,089 patients). Adjusted logistic regression was used to assess the association of treatment year with the annual percentage of patients who received hypofractionated RT (including 40-45 Gy/15 fractions, 34 Gy/10 fractions, or 25 Gy/5 fractions). Average annual percentage change (AAPC) was compared to determine if a significant change occurred in the use of hypofractionated RT during this period. Multivariable regression was used to determine factors associated with the use of hypofractionated RT. RESULTS Use of hypofractionated RT was stable between 2.5-3.3% from 2004-2008 and then monotonically increased to 22.2% by 2015 (p< 0.001). The AAPC in the use of hypofractionated RT was +29.6% per year (p< 0.001), with a corresponding decline in conventional fractionation over this period. No significant change was observed in palliative dosing schema or the use of stereotactic radiosurgery. On logistic regression, age, treatment at an academic center, Charlson Deyo score ≥2, and treatment year were significantly associated with utilization of hypofractionated RT. In this dataset, 24.8% of patients who received either conventional or hypofractionated RT died within 3 months of beginning RT. CONCLUSIONS During 2008-2015, an increasing number of elderly patients with glioblastoma received hypofractionated RT. Hypofractionated RT should be considered in elderly patients to shorten the time spent receiving medical care during the final months of life. Attention to hospice care is also important, especially in those with brief expected survival who may derive limited benefit from RT.

Prostate or Prostate Fossa Radiotherapy with or Without Dose-Escalated or Conventionally Dosed Pelvic Nodal Radiotherapy: Quality of Life Outcomes and Dosimetric Analysis

Background We measure the impact of pelvic lymph node radiotherapy (PLNRT) of two doses using conventional fractionation on long term quality of life (QOL) in prostate cancer. Methods Prostate cancer patients recorded baseline scores using the Expanded Prostate Cancer Index Composite (EPIC), prior to definitive or post-prostatectomy radiotherapy. If ENI was given, it was to 45 or 54 Gy. New scores were recorded 20–36 months after radiotherapy. Absolute change in each domain subscale and summary score was recorded as well as if this change met criteria for minimally important difference (MID), with separate multivariate analysis (MVA) for both measures. Subsequent dosimetric analysis was performed. Results Frequency of a MID decline was significantly greater in patients treated with ENI to 54 Gy for urinary function, incontinence, and overall. No urinary decline was correlated with PLNRT to 45 Gy. PLNRT to 54 Gy was significant for decline in urinary function, bother, irritative, incontinence, and overall score in one or both MVA models while 45 Gy was not. Postoperative status was significant for decline in urinary function, incontinence, and overall. Amongst postoperative patients, there was significantly greater decline in urinary function score in the salvage setting. Neither 54 nor 45 Gy significantly affected bowel subscale or overall score decline. Conclusions Using conventional fractionation, adding PLNRT to 54 Gy, but not 45 Gy, correlates with worse urinary QOL, with postoperative patients experiencing a steeper decline. PLNRT had no significant impact on bowel QOL with either dose.

Biologically Effective Dose and Rectal Bleeding in Definitive Proton Therapy for Prostate Cancer

Purpose and Objectives With increasing use of hypofractionation and extreme hypofractionation for prostate cancer, rectal dose-volume histogram (DVH) parameters that apply across dose fractionations may be helpful for treatment planning in clinical practice. We present an exploratory analysis of biologically effective rectal dose (BED) and equivalent rectal dose in 2 Gy fractions (EQD2) for rectal bleeding in patients treated with proton therapy across dose fractionations. Materials and Methods From 2016 to 2018, 243 patients with prostate cancer were treated with definitive proton therapy. Rectal DVH parameters were obtained from treatment plans, and rectal bleeding events were recorded. The BED and EQD2 transformations were applied to each rectal DVH parameter. Univariate analysis using logistic regression was used to determine DVH parameters that were significant predictors of grade ≥ 2 rectal bleeding. Youden index was used to determine optimum cutoffs for clinically meaningful DVH constraints. Stepwise model-selection criteria were then applied to fit a “best” multivariate logistic model for predicting Common Terminology Criteria for Adverse Events grade ≥ 2 rectal bleeding. Results Conventional fractionation, hypofractionation, and extreme hypofractionation were prescribed to 117 (48%), 84 (34%), and 42 (17.3%) patients, respectively. With a median follow-up of 20 (2.5-40) months, 10 (4.1%) patients experienced rectal bleeding. On univariate analysis, multiple rectal DVH parameters were significantly associated with rectal bleeding across BED, EQD2, and nominal doses. The BED volume receiving 55 Gy > 13.91% was found to be statistically and clinically significant. The BED volume receiving 55 Gy remained statistically significant for an association with rectal bleeding in the multivariate model (odds ratio, 9.81; 95% confidence interval, 2.4-40.5; P = .002). Conclusion In patients undergoing definitive proton therapy for prostate cancer, dose to the rectum and volume of the rectum receiving the dose were significantly associated with rectal bleeding across conventional fractionation, hypofractionation, and extreme hypofractionation when using BED and EQD2 transformations.

Neuro-ophthalmologic outcomes of standard versus hypo-fractionated stereotactic radiotherapy of AVPM

Background Most anterior visual pathway meningiomas (AVPM) are benign and slow-growing, but these tumors may affect visual functions, including visual acuity (VA) and visual field (VF). Due to location, most are treated non-surgically by fractionated stereotactic radiotherapy (FSRT), aiming to prevent tumor progression and visual functions deterioration. Unfortunately, FSRT in itself may affect visual functions. The current preferred treatment regimen (in terms of safety and effectiveness) is undetermined. While most cases are treated with conventional fractionation (cFSRT)—50.4–54 Gy in 28–30 fractions of 1.8–2 Gy, advances in technology have allowed shortening of total treatment length to hypofractionation (hSRT)—25-27 Gy in 3–5 fractions of 5–9 Gy. Our aim was to evaluate the association of radiotherapy regimen for treating AVPM (cFSRT vs. hSRT) with visual function outcomes (VA, VF) at the last neuro-ophthalmologic evaluation. Methods We conducted a retrospective cohort study of AVPM cases treated at Sheba Medical Center during 2004–2015. We compared cFSRT and hSRT regimens regarding visual function (VA, VF) outcomes at the last neuro-ophthalmologic evaluation. VA was determined by the logarithm of the minimum angle of resolution (LogMAR). VF was determined by the mean deviation (MD). A clinically relevant change in VA was defined as 0.2 LogMAR. Results 48 patients (13 receiving hSRT, 35 receiving cFSRT) were included, with a median follow-up of 55 months. No significant difference was evident regarding LogMAR or MD of involved eyes at the last evaluation. Six (17%) patients in the cFSRT group experienced clinically relevant VA deterioration in the involved eye, compared with six (46%) in hSRT (p = 0.06). Conclusion Our findings, using comprehensive and meticulous investigation of visual outcomes, suggest that hSRT may be associated with higher risk for VA and VF deterioration in AVPM especially in ONSM. We recommend the use of cFSRT for ONSM.

Dosimetric Evaluation of Oesophagus in Hypofractionated Supraclavicular Nodal Irradiation in Breast Cancer - A Retrospective Observational Study in a Tertiary Care Cancer Centre in Alappuzha, Kerala

BACKGROUND Acute esophagitis (AE) is a common toxicity seen in patients undergoing radiotherapy (RT) for breast cancer, which can affect their quality of life. Thus, majority of our patients receiving hypo fractionated dose of 40 Gy in 15 fractions were having AE. We conducted this study to evaluate the dosimetric parameters of oesophagus and correlate with published literature. METHODS Treatment plans of 80 post mastectomy patients who underwent radiotherapy for carcinoma of breast (Ca breast) with a dose of 40 Gy in 15 fractions to the chest wall along with supra clavicular fossa (SCF) were selected. Out of these, 44 patients (22 each in right and left side) were simulated in neck straight position and 36 in neck tilted position (18 each in right and left side). The oesophageal volume was contoured in already executed plans from the inferior border of cricoid cartilage to the inferior border of the SCF planning target volume (PTV). No plan modification was done after contouring the oesophagus. Dosimetric parameters like the maximum dose (Dmax) and mean dose (Dmean) to oesophagus, volume of oesophagus receiving ≥ 5 Gy (V5), ≥ 10 Gy (V10), ≥ 15 Gy (V15), ≥ 20 Gy (V20), ≥ 25 Gy (V25), ≥ 30 Gy (V30) were derived from dose volume histogram (DVH) data and analysed. RESULTS Dmean in straight neck group irrespective of side was 18.57 (± 7.30) Gy and in tilted neck 22.94 (± 9.53,) Gy, P = 0.023. Subgroup analysis shows Dmean was significantly high in patients with left sided disease than those with right sided disease (24.10 vs. 13.03, P = 0.00) in the straight neck cases. In the neck tilted group there was a nonsignificant increase in Dmean in left sided cases (25.36 vs. 20.53, P = 0.13). CONCLUSIONS Evaluation of oesophageal dosimetric parameters in hypofractionated dose showed that DmeanEQD2 was within the values of published studies in conventional fractionation. KEYWORDS Oesophageal Dosimetric Parameters, Breast Cancer

Short-term efficacy and long-term survival of limited-stage small cell lung cancer treated with large fractionation radiotherapy and conventional fractionation radiotherapy.

e20586 Background: Hyperfractionation (1.5Gy per dose twice a day, total dose 45Gy) or conventional fractionation (2Gy per dose once a day, total dose 60-70Gy) is the recommended dose fractionation for LS-SCLC. However, the optimal segmentation mode and dose of radiotherapy have not been determined. In this study, we evaluated the short-term efficacy and toxic and side effects of macrofractionation to explore the feasibility of macrofractionation radiotherapy in the treatment of LS-SCLC patients. Methods: From May 2011 to February 2020, 52 patients with LS-SCLC admitted to Jiangsu Cancer Hospital were retrospectively analyzed. The patients were divided into two groups according to the dose separation mode, including 29 cases in the large division group (3-4Gy per dose once a day, total dose 45-60Gy) and 23 cases (2Gy per dose once a day, total dose 50-68Gy) in the conventional division group. The short-term efficacy, 1-year survival rate and some other aspects of the two groups were compared. Results: The short-term overall response rate of large segmentation group was 79.3%, and there was significant difference compared with 52.2% of conventional segmentation group ( χ2 =4.293, P<0. 05) (Table). The 1-year survival rate of the large segmentation group was similar to that of the conventional segmentation group (82.8% vs．82.6%). The median survival time of large segment group was 30 months,which was not significantly different from the 34 months of conventional segment group (χ2=0.417, P>0.05). In terms of the effect of the two fractionated dose modes on long survival, 31.0% of patients in the large fractionation group survived more than 48 months, compared with only 13% in the conventional fractionation group. In addition, in the subgroup analysis of this study, it was found that compared with conventional fractionation radiotherapy, patients aged 45-65 years with ECOG score of 0-1 and lesions less than 5cm before radiotherapy could obtain more significant survival benefit from large fractionation radiotherapy, with statistically significant difference between the two groups (χ2=4.874, P<0.05). Conclusions: Large segmentation radiotherapy in the treatment of patients with LS-SCLC can improve the therapeutic effect and prolong the survival, especially for patients aged 45-65 years with ECOG score of 0-1 and lesions less than 5cm before radiotherapy , the survival benefit is more significant. In addition, large fractionated radiotherapy showed certain advantages in the long-term survival of patients with LS-SCLC, which is worthy of further clinical application.[Table: see text]

Radiosurgery treatment of Anterior Visual Pathway Meningioma (AVPM)

BACKGROUND Most anterior visual pathway meningiomas (AVPM) are benign and slow-growing, but these tumors may affect visual functions, including visual acuity (VA) and visual field (VF). Due to location, most are treated non-surgically by fractionated stereotactic radiotherapy (FSRT), aiming to prevent tumor progression and visual functions deterioration. Unfortunately, FSRT in itself may affect visual functions. The current preferred treatment regimen (in terms of safety and effectiveness) is undetermined. While most cases are treated with conventional fractionation (cFSRT) – 50.4–54 Gy in 28–30 fractions of 1.8-2 Gy, advances in technology have allowed shortening of total treatment length to hypofractionation (hSRT) – 25-27Gy in 3–5 fractions of 5–9 Gy. Our aim was to evaluate the association of radiotherapy regimen for treating AVPM (cFSRT vs. hSRT) with visual function outcomes (VA, VF) at the last neuro-ophthalmologic evaluation. METHODS We conducted a retrospective cohort study of AVPM cases treated at Sheba Medical Center during 2004–2015. We compared cFSRT and hSRT regimens regarding visual function (VA, VF) outcomes at the last neuro-ophthalmologic evaluation. VA was determined by the logarithm of the minimum angle of resolution (LogMAR). VF was determined by the mean deviation (MD). A clinically relevant change in VA was defined as 0.2 LogMAR. RESULTS 48 patients (13 receiving hSRT, 35 receiving cFSRT) were included, with a median follow-up of 55 months. No significant difference was evident regarding LogMAR or MD of involved eyes at the last evaluation. Six (17%) patients in the cFSRT group experienced clinically relevant VA deterioration in the involved eye, compared with six (46%) in hSRT (p = 0.06). CONCLUSION Our findings, using comprehensive and meticulous investigation of visual outcomes, suggest that hSRT may be associated with higher risk for VA and VF deterioration in AVPM especially in ONSM. We recommend the use of cFSRT for ONSM.

AN OBSERVATIONAL STUDY TO EVALUATE THE RESPONSE AND TOXICITY WITH CONVENTIONAL FRACTIONATION AND HYPO FRACTIONATED RADIOTHERAPY FOR LOCALLY ADVANCED NON SMALL CELL LUNG CARCINOMA FOLLOWING INDUCTION CHEMOTHERAPY

Aims & Objectives: To evaluate the response and toxicity with Conventional fractionation and hypofractionated radiotherapy for locally advanced NSCLC following induction chemotherapy. To assess and compare following for locally advanced NSCLC with Conventional and hypo fractionated radiotherapy following induction chemotherapy. Materials And Methods: This prospective observational study was conducted at Saroj Gupta Cancer Centre and Research Institute, Kolkata; accrual was from June 2016 to September 2017. Data was collected from all patients who had been cytological / histopathologically and radiological proven stage III Non Small Cell Lung Carcinoma; fullling eligibility criteria, were recruited after obtaining informed consent. Results And Analysis: We found that the association between response at the END OF RT in two groups was not statistically signicant (p=0.8559). Association between Dermatitis highest grade at end of RT in two groups was not statistically signicant (p=0.5201). Association between Response 6 months after RT in two groups was not statistically signicant (p=0.7667). Association between Response 9 months after RT in two groups was not statistically signicant (p=0.9255). Association between Dermatitis. Conclusion & Summary: Our study showed hypofractionated radiotherapy is non-inferior to Conventional radiotherapy with equivalent overall response and toxicity and well tolerable. In patients with poor performance status who cannot tolerate concurrent chemo radiation, induction chemotherapy with hypofractionated radiotherapy regimen can be considered as a treatment of choice with manageable toxicities.