Curative RT Research Articles

EP.13C.08 Leukoencephalopathy and Brain Metastasis in LS-SCLC Patients with and without PCI after Curative Thoracic RT

EP.13C.08 Leukoencephalopathy and Brain Metastasis in LS-SCLC Patients with and without PCI after Curative Thoracic RT

Dental Extractions Before Radiation Therapy and the Risk of Osteoradionecrosis in Patients With Head and Neck Cancer

Patients with head and neck cancer undergo extraction of teeth with poor prognoses to minimize post-radiation therapy (RT) extractions, which are known to cause osteoradionecrosis (ORN). However, many patients are required to start RT before the extraction sites are completely healed. The role of pre-RT extractions in the development of ORN has been disputed in literature. To determine whether the timing of pre-RT dental extractions is associated with ORN development in patients with head and neck cancer. This retrospective cohort study was conducted at a single institution (Princess Margaret Cancer Centre, Toronto, Canada) between January 1, 2011, and January 1, 2018, and included 879 patients with head and neck cancer who underwent pre-RT dental extractions before curative RT of 45 Gy or greater. Patient demographic information and clinical characteristics (eg, primary cancer site, nodal involvement, chemotherapy, smoking status, dental pathology) were considered. Data analyses were performed from July to December 2022. Timing (number of days) from dental extractions to RT start date and pre-RT extractions categorized as healed, minor bone spicules (MBS), or ORN. The study population consisted of 879 patients with a median (range) age of 62 (20-96) years, with 685 men (78%) and 194 women (22%). Of these, 847 (96.3%) healed from pre-RT dental extractions, 16 (1.8%) developed MBS, and 16 (1.8%) developed ORN. The median (range) time in number of days from pre-RT extraction(s) to start of RT was 9 (0-98) days in the healed cohort, 6 (3-23) days in the MBS cohort, and 6 (0-12) days in the ORN cohort. There was a large difference in the timing of pre-RT extractions between the healed and the MBS cohorts (mean 11.9 vs 7.4 days to radiation; difference 4.4; 95% CI, 1.5-7.3), and the healed and the ORN cohorts (mean 11.9 vs 7.1 days; difference 4.8 days; 95% CI, 2.6-7.1). The findings of this retrospective cohort study suggest that there was an important association between the timing of pre-RT dental extractions and ORN when extractions occurred within 7 days of the RT start date. Despite this, ORN after pre-RT extractions is relatively rare. These findings indicate that patients with head and neck cancer who are to undergo RT should not delay treatment for extractions when it might compromise oncologic control.

PO-1488 Local recurrence of prostate cancer after curative RT: the role of salvage SBRT re-irradiation

PO-1488 Local recurrence of prostate cancer after curative RT: the role of salvage SBRT re-irradiation

PO-2102 CT-based radiomics for outcome prediction in oropharyngeal cancer patients treated with curative RT

PO-2102 CT-based radiomics for outcome prediction in oropharyngeal cancer patients treated with curative RT

The Effect of the Time Interval between Temozolomide and Radiotherapy in Adjuvant High-Grade Glioma Treatment

<h3>Purpose/Objective(s)</h3> The standard of care for high grade glioma (HGG) treatment consists of postoperative radiotherapy and temozolamide (TMZ). The effect of time between TMZ administration and RT on treatment outcomes is not well defined. The purpose of this study was to examine the interval between oral administration of TMZ and RT, and its effect on treatment outcomes in patients with HGG. <h3>Materials/Methods</h3> The clinical data of 277 patients with HGG treated between 2009 – 2021 at four centers were retrospectively analyzed. The following are the inclusion criteria: Pathologically proven grade ≥3 glial tumors, ≥18 years old, and completion of curative RT with concurrent oral 75 mg/m²/day TMZ. Patients who were unable to take oral TMZ, or had previously been treated with TMZ and/or RT were excluded. The TMZ to RT interval (TRI) was calculated from the time of oral TMZ administration to the time of RT fraction. In relation to the TMZ half-life, the interval time was divided into <2 h and ≥2 h groups. Progression free survival (PFS) is calculated as the time between the end of RT and clinical or radiological progression. Overall survival (OS) is calculated from the time of diagnosis to the last follow-up. <h3>Results</h3> The median age was 58 years (range: 19–81). 159 patients (57.4%) were male, while 118 (42.6%) were female. 75.4% of patients had an ECOG performance score (ECOG PS) of 0–1, and 54.5% had gross total resection (GTR). The median fraction and total RT doses were 2 Gy (1.8–3) and 60 Gy (40–60), respectively. The median follow-up was 15.2 months (range: 1.9–75.1) for the entire cohort. Two-year OS and PFS rates were 35% and 15%, respectively. After completion of RT, disease progression occurred in 255 patients (92.1%) at a median of 6.4 months (range, 0.2–64.9). The 2-year OS was 42.8% for patients with a TRI >2 hours and 32% for patients with a time interval of ≤2 hours (p = 0.18). Similarly, there was no statistically significant difference in 2-year PFS between the two groups (12.8% vs. 9%; p = 0.95). Age, ECOG PS, and type of surgery were all significant prognostic factors for OS and PFS in univariate analysis. In multivariate analysis, advanced age [HR = 1.03 (95% CI, 1.01 – 1.04); p<0.001], poor ECOG PS [HR = 2.14 (95% CI, 1.56 – 2.94); p<0.001], and incomplete surgical resection [HR = 1.39 (95% CI, 1.06–1.84); p = 0.02] were independent predictors of poorer OS. Similarly, age [HR = 1.02 (95% CI, 1.01 – 1.03); p = 0.002], ECOG PS [HR = 1.57 (95% CI, 1.17 – 2.09); p = 0.002], and type of surgery [HR = 1.41 (95% CI, 1.10 – 1.80); p = 0.006] were all significant prognostic factors for PFS in multivariate analysis. <h3>Conclusion</h3> We found that advanced age, poor performance status, and incomplete surgical resection were all predictive of poor OS and PFS in this current study. However, we were unable to detect a statistically significant effect of the time interval between oral administration of TMZ and RT. Validation of our findings will require a longer follow-up period and randomized trials.

PD-0413 Outcomes in pelvic versus common iliac node positive prostate cancer treated with curative RT

PD-0413 Outcomes in pelvic versus common iliac node positive prostate cancer treated with curative RT

Definitive and adjuvant radiation therapy for external auditory canal and temporal bone squamous cell carcinomas: Long term outcomes

IntroductionPrimary Squamous Cell Carcinoma (SCC) of the external auditory canal (EAC) and Temporal Bone (TB) are rare entities with very few large reports on outcomes and toxicities. Materials and methodsA retrospective audit of all SCC of EAC/TB tumors treated with curative intent RT at our Institute between January 2007 and December 2019 was undertaken. The primary endpoint of the study was event-free survival (EFS). ResultsEighty-nine patients were eligible for analysis. The median age was 54 years. The median follow-up of surviving patients was 61 months. Sixty-five patients received adjuvant RT, and 24 received definitive RT. Neoadjuvant Chemotherapy for aiding resectability was used in 12 patients, out of which 8 underwent surgery. The 5-year LRC, EFS, and OS were 66.2%, 57.8%, and 63.5%. The predominant pattern of failure was local (n = 36, 40.4%). Regional failure was seen in only five patients, none of which were in patients in whom elective nodal irradiation had been omitted post-operatively. On multivariable analysis adjuvant RT was associated with superior outcomes than definitive RT. Treatment with IMRT resulted in lower ≥ grade 2 late subcutaneous fibrosis (8.7% vs. 38.1%) compared to conventional/3D-CRT technique. ConclusionsSurgery followed by adjuvant therapy should remain the mainstay of treatment for EAC and TB SCC. IMRT should be the preferred modality for RT due to lower late morbidity. Elective nodal irradiation is routinely not warranted in the adjuvant setting for EAC and TB squamous cell carcinomas.

PH-0048 Pattern of failure after curative (C-)RT in HNSCC: data from the phase III DAHANCA19 study

PH-0048 Pattern of failure after curative (C-)RT in HNSCC: data from the phase III DAHANCA19 study

Prognostic Factors Predict Oncological Outcome in Older Patients With Head and Neck Cancer Undergoing Chemoradiation Treatment.

PurposeOlder patients with head and neck cancer (HNC) represent a challenging group, as frailty and comorbidities need to be considered. This study aimed to evaluate the efficacy and side effects of curative and palliative (chemo) radiation ([C]RT) with regard to basic geriatric screening in older patients.MethodsThis study included HNC patients aged ≥70 years who were treated with curative or palliative (C)RT. Clinicopathological data including Charlson Comorbidity Index (CCI), Karnofsky performance status (KPS), and treatment data were analyzed as predictors of overall survival (OS).ResultsA total of 271 patients (median age, 74 years) were enrolled. The majority had UICC stage III/IV (90%) and underwent curative treatment (85.2%). A total of 144 (53.1%) patients received definitive and 87 (32.1%) had adjuvant (C)RT. Overall, 40 patients (14.8%) received palliative (C)RT. Median follow-up duration (curative setting) was 87 months, and the 2- and 5-year OS rates were 57.8 and 35.9%, respectively. Median OS was significantly different for age ≤75 vs. >75 years, CCI <6 vs. ≥6, KPS ≥70 vs. <70%, Tx/T1/T2 vs. T3/T4, and adjuvant vs. definitive (C)RT, respectively. Age 70–75 years (p = 0.004), fewer comorbidities when CCI < 6 (p = 0.014), good KPS ≥ 70% (p = 0.001), and adjuvant (C)RT (p = 0.008) independently predicted longer survival. Palliative RT resulted in a median OS of 4 months.ConclusionOlder age, lower KPS, higher CCI, and definitive (C)RT are indicators of worse survival in older patients with HNC treated curatively. Without a comprehensive geriatric assessment in patients aged >75 years, the KPS and CCI can be useful tools to account for “fitness, vulnerability or frailty” to help in treatment decision-making.

Rectum Dose-Volume Histogram (DVH) Parameters And Patient-Reported EPIC-Bowel Domain For Patients Undergoing Radiotherapy (RT) For Prostate Cancer (PC): A Single-Center Prospective Registry Experience

Prostate cancer therapy toxicities can affect QOL. We report one of the first analyses of rectal dose and changes in QOL measured with the EPIC bowel domain in PC patients treated with curative intent RT in a large, single-institution prospective registry. Two hundred fifty-two pts with localized PC were treated with curative intent RT from 2016- 2018 on an IRB approved prospective registry. The Expanded Prostate Cancer Index Composite (EPIC) health-related QOL instrument was administered at baseline, end-of-treatment, 3, 6, 12 months (m), and then annually. A higher EPIC score implies less bowel symptom burden. DVH parameters for the rectal structure were computed, Dx was the dose (Gy) to a % of the rectum and Vx was the % volume receiving a given dose (Gy). Rectal dose was analyzed using BED (alpha/beta = 3), EQD2Gy, and total dose. In order to determine optimal cut-points to find clinically meaningful DVH, we utilized logistic regression and defined the ‘best’ cut-point to be the value that maximized Youden’s Index. Repeated measures mixed models were then implemented to determine the effect of patient, clinical, and treatment factors (including DVH) on patient-reported bowel symptom burden (EPIC-Bowel). Median follow-up was 20mo(range:2.5–40), pre-RT PSA = 6.12(1.3–129), T Stage T1c(T1b–T3b), Gleason Score 7(range 6-10), and 99% N0. The median prescribed dose was 70Gy (38–79.2) in 5 to 44 fractions. Standard fractionation (1.8-2Gy) was used in 120 pts (48.2%), moderate hypofractionation (2.5-3Gy) in 87 pts (35.1%), and extreme hypofractionation (>6Gy) in 42 pts (16.7%). Globally, treatment had minimal effect over EPIC-bowel scores which remained unchanged over time, with a median baseline = (96.4), end-of-treatment = (94.6), 3mo = (95.4), 6mo = (96.4), 12m = (94.6), and 24m = (96.4). However, rectal dose affected QOL with the strongest DVH signals noted for BED V51Gy and EQD2 V22Gy—with an optimal cut-point of 14.4% and 16.4%, respectively. On multivariate modeling BED V51Gy >14.4% was significantly associated with a decline of the epic bowel domain of 2.1 points (p = 0.01), and an EQD2 V22Gy >16.4% was significantly associated with a decline of 2.3 points (p<0.003). Rectal dose, specifically BED V51Gy>14.3% and EQD2 V22Gy>16.4%, are significantly associated with decline in bowel related QOL in patients undergoing definitive RT for localized PC. This is one of the first studies to examine rectal dose and correlate them to patient reported treatment related QOL.

Refining assessment of response to radiation-based therapy for muscle-invasive bladder cancer: Is post-treatment tumor bed biopsy always necessary?

IntroductionRadiation-based therapy (RT) has emerged as a suitable alternative to radical cystectomy (RC) and pelvic lymph node dissection for muscle-invasive bladder cancer (MIBC) patients. Routine biopsy after RT to rule out residual disease remains inconsistent across guidelines. Our objective was to review the significance of a bladder biopsy in terms of assessment of response post-RT and its potential impact on survival. Patients and methodsThis was a single-center retrospective study on patients with MIBC (cT2-4aN0-2M0) treated with curative intent RT. A total of 169 patients with primary urothelial carcinoma were analyzed. Patients’ demographic, clinical and pathological variables, imaging, cystoscopy, urine cytology, and biopsy reports after RT were collected and compiled. Whenever urine cytology was positive or cystoscopy showed any malignant-appearing lesion, the first assessment post-RT was considered suspicious for residual disease. A descriptive population analysis was reported. Cox regression multivariable analysis was performed to identify independent variables associated with survival outcomes. ResultsMedian age was 75 years (interquartile range 66–82) and clinical staging was cT2 in 152 (90%) patients. Cytology and cystoscopy were normal in 140 (83%) after RT. Of patients with a control biopsy, residual MIBC was present in 3 (5%) and non-MIBC in another 6 (11%). On the contrary, a for-cause biopsy due to a suspicious assessment post-RT did not yield residual cancer in 45% of patients. Multivariable analysis showed that age (hazard ratio [HR] 1.04, P< 0.001), lymphovascular invasion (HR 1.68, P = 0.03) and a suspicious assessment after RT (HR 3.21; P< 0.001) were significantly associated with worse OS. This study was limited by its retrospective design. ConclusionsA routine biopsy after RT may be warranted to assess treatment response. This might be particularly important for patients who may benefit from early surgical intervention for residual MIBC. Further prospective studies are needed to confirm our findings.

Radiation Therapy in the Hispanic Breast Cancer Population: An Analysis of Patient Demographics and the Impact of Insurance Status on Rates of Breast Conserving Radiation Therapy.

Disparities in minority healthcare include lower rates of insurance coverage and increased morbidity and mortality from cancer. We sought to evaluate the demographics of our Hispanic breast cancer population and evaluate the impact of insurance status on rates of breast conserving radiation therapy (BCT) including whole breast radiation (WBRT) and accelerated partial breast irradiation (APBI) versus postmastectomy radiation therapy (PMRT). We performed a retrospective review of 120 women with invasive and non-invasive breast cancer receiving curative RT between the dates of January 2017 through June 2019. Women identifying as Hispanic and all women from Latin America were included. BCT included WBRT with 3D-conformal RT (3D-CRT) and APBI with either 1. 3D-CRT or 2. HDR 192Ir brachytherapy interstitial catheters or surface applicators. We defined insurance status as 1. Insured, 2. Medicaid and 3. Non-insured. Additional patient demographics including age, BMI, country of birth, and anatomical stage were reviewed. Multivariable logistic regression model was used to evaluate odds ratios for primary outcome of WBRT/APBI as a BCT event vs. PMRT. 70 Hispanic women were identified for analysis. Median age, insurance status and cancer stage are listed (Table 1). The median BMI was 29.7 (22.0, 45.3) and median age was 58.5 (33.0, 81.0). The median BMI was non-significant but slightly lower in PMRT group (29.7 vs. 30, p-value = 0.82). Multivariable model was constituted with variable: age, BMI, primary insurance, anatomic stage, and country/region of birth (USA, Caribbean, and South/Central America). There were 58 BCT events (49 WBRT and 9 APBI) which explains enough power to construction of multivariable model. In a multivariable model, the insured subjects had 17.5 times higher odds of opting for WBRT/APBI BCT [OR (95% CI) = 17.53 (1.69, 432.0)] compared to non-insured subjects which was statistically significant (p = 0.036). This association was significant [OR (95% CI) = 6.36 (1.44, 34.37), p = 0.019] in a single variable model with more than 6 times higher odds. All other associations in the multivariable model were not statistically significant. Hispanic women comprise the majority of breast cancer patients treated at our community hospital with 83% receiving BCT versus PMRT. Insured status was a significant predictor of BCT with the insured population having an almost 18-fold higher rate of receiving WBRT or APBI than the non- insured population (OR = 17.53). Although this is a single institution study and limited by a small PMRT sample size, this health care disparity warrants further investigation to better understand access to care and barriers to BCT in the Hispanic population.Tabled 1Abstract 2925; TableWBRT/APBI n = 58PMRT n = 12All n = 70Age59.553.558.5Insured35338Medicaid12315Non-insured11617Stage 010010Stage I27027Stage II181028Stage III325 Open table in a new tab

Retrospective cohort study of unresectable stage III non-small-cell lung cancer in Canada.

The management of unresectable stage iii non-small-cell lung cancer (nsclc) is complex and best determined through multidisciplinary consultation. A longitudinal, population-level study was carried out to describe the management approach and outcomes of treatment in the real-world setting in Ontario. Individuals diagnosed with nsclc between 1 April 2010 and 31 March 2015 were identified in the Ontario Cancer Registry. Unresectable disease was defined as no surgery reported within 3 months of diagnosis. Initial treatments included radiotherapy (rt, curative or palliative), chemotherapy, targeted therapy, and chemoradiation [crt, concurrent (ccrt) or sequential (scrt)]. Survival was calculated from diagnosis with stage iii disease to death or last follow-up. Of the 24,729 individuals diagnosed with nsclc, 5243 (21.2%) had stage iii disease, with most of the latter group (4542, 86.6%) having unresectable disease. Median age was 70 years, and 54.2% were men. The frequency of first-line treatment was ccrt, 22.1%; palliative rt, 21.0%; curative rt, 19.6%; no treatment, 19.6%; chemotherapy alone, 11.6%; scrt, 5.4%; and targeted therapy, 0.7%. Median overall survival (mos) was 14.2 months [95% confidence interval (ci): 13.6 months to 14.7 months], with the longest survival observed in patients who received targeted therapy (mos: 34.7 months; 95% ci: 21.4 months to 51.2 months), and the poorest, in those receiving no cancer treatment (mos: 5.9 months; 95% ci: 5.0 months to 6.4 months). The mos in patients receiving ccrt was 23.6 months (95% ci: 21.4 months to 25.6 months). Guideline-recommended ccrt is undertaken in only a small proportion of patients with unresectable nsclc in Ontario. The reasons for low uptake of that recommendation are only partly understood.

Population-based analysis of curative therapies in stage II non-small cell lung cancer: the role of radiotherapy in medically inoperable patients

ObjectivesCurative intent therapy of stage II NSCLC may include surgical resection or definitive radiotherapy. Primary management with surgery or radiotherapy may be influenced by patient and disease characteristics. We sought to perform a comparison of patients receiving surgery or radical radiation therapy as their curative treatment, and explore the impact of known prognostic factors on outcome.Materials and methodsA retrospective review was completed of all patients with stage II NSCLC referred to the BC Cancer Agency from 2005 to 2012. Cases were filtered to identify those receiving curative intent therapy including surgery or radiotherapy. Information was collected on known prognostic and predictive factors. The primary outcome measure was overall survival. We compared survival among patients receiving curative intent radiotherapy versus surgical intervention.ResultsA total of 535 patients were referred. Of these, 245 (46%) received curative intent surgery, 132 (25%) curative intent radiotherapy, and 158 (30%) did not receive curative therapy. There were significant differences between cohorts with respect to median age, histology, ECOG PS, smoking status, and weight loss. Median OS was significantly different between cohorts: 61.4 m surgery, 26.5 m curative RT, and 13.1 m non-curative therapy. In a case-matched analysis, median OS remained superior for surgery at 101.6 m vs 28.1 m for curative RT. In a multivariate analysis, ECOG PS, weight loss, and treatment cohort all influenced survival. Among patients receiving curative intent radiotherapy, the use of concurrent chemotherapy and RT dose > = 60Gy were associated with improved outcomes.ConclusionsAmong patients with stage II NSCLC, many are unable to undergo standard of care surgical resection. Radiotherapy provides an inferior yet still curative option in the management of inoperable patients. Further work is needed to optimize outcomes in this population.

Outcomes of 210 Patients with Follicular and Marginal Zone Lymphomas Treated with 4 Gy of Radiation Therapy

Introduction Indolent lymphomas, such as follicular lymphoma (FL) and marginal zone lymphoma (MZL), are highly radiosensitive and often respond to very low dose radiation therapy (VLDRT). We investigated the outcomes of patients treated with 4 Gy from a large, contemporary, real world cohort, and a subset of potentially curable (PC) patients with early stage (Ann Arbor stage I-II) disease and no prior therapy to the targeted lesion(s) before VLDRT. Methods We analyzed 256 treated sites from 210 consecutive adult patients (Table 1) with FL or MZL who were treated with VLDRT of 2 Gy x 2 fractions between 2006 and 2019 at our comprehensive cancer center. Initial overall response rate (ORR) was defined as complete response (CR) or partial response (PR) using Lugano criteria at first follow-up post-RT (median: 2.1 months; Interquartile range: 1.6-2.5 months). Stable disease (SD) or progressive disease (PD) at 2 months post-RT were considered local failure (LF). Freedom from local failure (FFLF) was defined as time from VLDRT to LF. Patients were censored at the start of a subsequent line of therapy if the VLDRT-treated site had not progressed. Event-free survival (EFS) was calculated per patient from VLDRT to LF or distant PD. FFLF and EFS were estimated using Kaplan-Meier and compared using log-rank. Results Initial ORR for all sites was 88% (CR: 65%, PR: 23%); 12% (n=31) were initially nonresponding (SD: 7%, PD: 5%). Thirteen sites with initial PR/SD/PD received additional RT (median: 30 Gy) within 6 months of VLDRT and had subsequent CR (n=7), PR (n=5), and PD (n=1). With median follow-up of 21 months, 2-year FFLF was 70%. Initial response to VLDRT was prognostic with a significantly improved 2-year FFLF for sites with CR (n=166) compared to those with PR (n=58) (88% vs. 66%, p&lt;0.001). There was improved 2-year FFLF for extranodal versus nodal disease (81% vs. 58%, p=0.001) but not for previously untreated versus relapsed/refractory (76% vs. 68%, p=0.12) or early versus advanced stage sites (72% vs. 68%, p=0.98). In the subset of PC patients (n=50), there were 52 lesions. The histology of these sites was split between FL (n=21, 41%), MZL (n=22, 42%) and indolent lymphoma not further classified (n=9, 17%). The majority of the lesions in the PC cohort were extranodal (n=42, 81%). Median follow-up was 1 year with a 1-year EFS of 82%. Of the 12 PC patients who progressed post VLDRT, two thirds developed a distant site of recurrence outside of the VLDRT field. In field recurrence alone was rare (n=4). Diffuse large B cell lymphoma transformation after VLDRT was rare in the PC (n=0) and overall (n=6, 3%) cohort; all cases of transformed DLBCL were diagnosed out of VLDRT field. Conclusions Overall, patients with FL and MZL treated with only 4 Gy have excellent initial ORR. Upfront CR is prognostic of improved disease control. Early evaluation following VLDRT identifies nonresponders who may benefit from additional RT and spares many patients from higher doses of RT with durable local control. Our analysis of PC patients suggests that VLDRT does not compromise the standard curative RT approach. Disclosures No relevant conflicts of interest to declare.

Treatment Outcomes and Survival Following Primary (chemo) Radiotherapy in HPV+ Oropharynx Cancer: A Largescale Comparison of Two Institutions

We compared outcomes in two well-defined, population based cohorts of HPV+ oropharynx cancer (OPC) patients (pts) treated with curative (chemo) RT. All non-metastatic HPV+ OPC treated between 2007 –2015 with definitive IMRT ± chemotherapy in two distinct cohorts were included: one was nationwide (C1) and the other institutional (C2), the latter representing one of two cancer centers within a population district and received 80% of the region’s referrals. HPV status was determined using p16-IHC staining. Outcomes were compared between the two cohorts. Actuarial rates of locoregional control (LRC), ultimate LRC (including surgical salvage), and distant control (DC), were estimated by competing risk method. Disease free survival (DFS) and overall survival (OS) were estimated using Kaplan-Meier method. Multivariable analyses (MVA) with Cox regression calculated hazard ratio (HR) adjusted for age, gender, performance status (PS), T- and N-category (8th Edition TNM), treatment schedule, and smoking. A total of 1875 pts were included. C1 pts (n=1174) were treated according to nationwide guidelines: all received moderately accelerated fractionation (6fx/week), 96% (1129) received Nimorazole (a hypoxia modifier) and 73% (856) concurrent weekly Cisplatin. C2 pts (n=701) were treated according to institutional protocols: 69% (481) received concurrent bolus Cisplatin with 5 fx/week RT, while 9% (60) and 23% (160) received 5 fx/week and 6 fx/week RT alone, respectively. No C2 pts received Nimorazole. Median follow-up was 4.8 years. Age and PS did not differ between cohorts. Compared to C2, more C1 pts were female (24% vs 16%, p<0.001), had lower T-category (T1-2: 77% vs 56%, p<0.001), N-category (N0-N1: 77% vs 66%, p<0.001), and stage group (stage I: 63% vs 44%, p<0.001), and were heavier smokers (p<0.001). Compared to C2, C1 pts had reduced actuarial probability of 5-year LRC (87% vs 93%, with adjusted HR by MVA=0.47 [95% CI: 0.33-0.67]) and Ultimate LRC (94% vs 96%, HR=0.52 [0.33-0.82]). DC (93% vs 88%, HR=1.31 [0.95-1.82]) and DFS (81% vs 77%, HR=1.17 [0.93-1.48]) did not differ significantly between C1 and C2 cohorts, whereas OS (85% vs 80%, HR=1.29 [1.0-1.67], p=0.054) approached statistical significance. T- and N-category and chemotherapy retained independent prognostic impact for all outcomes, and heavy smoking negatively impacted LRC (HR=1.57[1.07-2.31]), DFS (HR=1.62[1.22-2.16]) and OS (HR=1.89[1.36-2.62]). This pooled analysis of two population based cohorts confirms the good outcome and survival of HPV+ OPC following definitive (chemo) RT. The observed differences in RT outcomes between the cohorts probably reflect differences in treatment strategies as well as tumor and patient characteristics (including smoking status), although DFS and OS remained comparable.

Chemoradiotherapy for anal cancer: A population-based study of treatment interruption, treatment completion, and associated outcomes.

3573 Background: Chemoradiotherapy (CRT) is the standard treatment for squamous cell anal carcinoma (SCCA). Here, we describe CRT delivery in routine practice and explore the association between treatment interruption, non-completion and outcomes. Methods: The Ontario Cancer Registry was used to identify all incident cases of SCCA treated with curative intent RT in Ontario, Canada (2007-2015). Treatment interruption was defined a priori as &gt; 7 days between consecutive fractions. Completed CRT was defined as receiving ≥50 Gy and 30+ fractions of RT along with 2 concurrent doses of chemotherapy. Log-binomial regression models were used to estimate risk ratios (RR) between patient characteristics and 1) failure to complete CRT and 2) salvage abdominoperineal resection (APR). Cox proportional hazard models were used to estimate hazards ratios (HR) between treatment interruption or non-completion and 1) cancer specific survival (CSS) and 2) overall survival (OS). Results: We identified 1593 patients with SCCA; 73% (n = 1161) initiated curative intent RT. Median RT dose and duration was 54 Gy (IQR, 50.4-67.8) and 46 days (IQR, 42-53), respectively. Treatment interruption &gt; 7 days occurred in 23%. CRT was completed by 59%. Factors associated with CRT non-completion were age &gt; 70 vs. &lt; 50 (RR 0.70, 95% CI: 0.59-0.93) and greater comorbidity (1+ vs. 0, RR 0.57, 95% CI: 0.39-0.85). Treatment interruption &gt; 7 days appears to be associated with salvage APR (RR 1.39, 95% CI: 0.91-2.12). In an exploratory analysis, the association between treatment interruption &gt; 10 days and salvage APR reached statistical significance (RR 1.63, 95% CI, 1.06-2.53). Treatment interruption was not associated with inferior CSS (HR 0.87, 95% CI: 0.60-1.25) nor OS (HR 0.96, 95% CI: 0.76-1.23). Failure to complete CRT was not associated with higher rates of salvage APR nor inferior CSS, but was associated with inferior OS (HR 1.40, 95% CI: 1.13-1.72). Conclusions: In routine clinical practice, treatment interruption and non-completion among patients with SCCA are common. Quality improvement initiatives to optimize treatment continuity and completion are needed. The observed association between failure to complete CRT and OS is likely a reflection of confounding by indication, which is highlighted by the lack of association between CRT completion and CSS. Publisher's Note The abstract by Raphael et al entitled, “Chemoradiotherapy for anal cancer: A population-based study of treatment interruption, treatment completion, and associated outcomes,” published in the Journal of Clinical Oncology 37, no. 15 suppl (May 20 2019) 3573–3573, contained errors. In updated analyses, the authors discovered that the main exposure (radiation therapy) may have been incorrectly coded into the population-level databases from several individual treatment centers. Some of the coded radiation doses and fractionation numbers are considerably beyond what would be clinically plausible. Until this issue has been resolved, the authors believe the results of their study cannot be considered reliable. This article was retracted on 17-07-2019.

P1.12-10 Patterns of Curative Chemo-Radiotherapy Regimen and Impacts on the Outcome of Limited Stage SCLC in a Canadian Institution: 2010 – 2015 Diagnoses

Curative intent chemotherapy and radiotherapy (ChemoRT) is the widely recommended treatment for limited stage (LS) small cell lung cancer (SCLC) follow by prophylactic cranial irradiation (PCI) in those who responded to the initial therapy. LS-SCLC is however characterized by high relapse rate with only about 20% surviving to 2 years. Our objective is to examine the characteristics, treatment patterns and overall survival of LS-SCLC for patients diagnosed within a 5-year period at the Tom Baker Cancer Centre, Canada, prior to wide adoption of emerging treatment options including surgery and immunotherapy in the curative and palliative settings respectively. Using the Glans-Look Lung Research (GLR) database, we defined the clinical and demographic features of patients diagnosed with LS-SCLC from 2010 to 2015, determined the rate of systemic treatment uptake, and investigated the impact of PCI, curative intent, and palliative treatments on overall survival. We summarized our findings with descriptive statistics (including Fisher’s Exact test) and Kaplan Meier survival curves using SPSS. Statistical significance was set at p value < 0.05 and 95% confidence intervals. About a third (107/349, 31%) of patients diagnosed with SCLC from 2010 to 2015 were LS-SCLC, with median age of 67 years. Over the 5-year period, systemic treatments uptake rates and patterns fluctuates. Overall, > 50% received ChemoRT and 65% of the ChemoRT group also received PCI. Curative concurrent RT dose 45 – 55Gy, 25 fractions schedule was more common (55%). Few stage T1a-2a, N0-1 LS-SCLC had surgery (5%). Thirty eight percent of those who received initial curative intent treatments further received some palliative treatments for disease recurrence or progression {8% (2/26) initial Surgery ± Adjuvant and 92% (24/26) ChemoRT}. The median overall survival for the cohort was 24 months (p < 0.001). There were more than 50% survival at 60 months for patients treated with curative 15 fractions concurrent ChemoRT (p < 0.001). Most patients received ChemoRT while a few had surgery. Concurrent 15 fractions ChemoRT may offer better survival benefits than the 25 fraction schedule. The impact of PCI on LS-SCLC and other survival outcomes will be presented.

Discontinuation of Curative Head and Neck Irradiation: Etiologies and Outcomes

There is scarcity of valid clinical data on survival after premature discontinuation of curative radiation therapy (PDCRT) for head and neck (H&N) cancers. This makes it challenging to advise patients seeking to withdraw from treatment early. In this study, we aimed to characterize causes of PDCRT and assess overall survival in this subset of patients A total of 1176 patients received H&N radiation therapy at our institution in the period 2010-2017. Of these patients, 59 (5%) were unable to complete a full course of prescribed curative RT and were included in the analysis. Mean follow-up time was 18 months (0-81.9 months). Primary endpoints were causes of PDCRT and overall survival (OS). PDCRT causes were classified into five categories: discontinuation against medical advice (DAMA), medical comorbidity, RT toxicity, disease progression, and social factors. Survival was examined using the life-table method and log-rank test. DAMA (32%), medical comorbidity (24%), and RT toxicity (18%) accounted for the majority of PDCRT causes. Of 59 analyzed patients, most were men (80%), ≥60 years old (59%), white (68%), lived ≥ 10 miles from hospital (61%), were undergoing a longer (definitive) course of RT (59%), and receiving bilateral neck irradiation (70%). At the same time, the majority of patients had ECOG ≤1 (78%) and ≤1 comorbidities (56%) at the start of the treatment. Most common primary sites were oropharynx (37%), larynx (20%), and oral cavity (12%). During RT, 66% of patients had treatment interruptions and 34% required inpatient admission. Supportive Oncology service was involved in care of only 20% patients on treatment. Radiation Therapy Oncology Group grade ≥2 dysphagia was observed in 47% patients, mucositis in 46%. Median prescribed dose was 69.96 Gy (range, 50-72 Gy). Median completed radiation dose was 50.9 Gy (range, 2-68 Gy). At the time of analysis, 25 (42%) deaths were recorded. Two-year and 4-year OS rates was 56% and 43%. There was a trend toward improved survival with total completed dose ≥ 50 Gy vs < 50 Gy, 67% vs 40% (P=.06). To the best of our knowledge, this is the largest modern study examining clinical outcomes after PDCRT. The principal reason for treatment withdrawal remains DAMA, and hence more effort need to be focused on educating and providing support to meet the unique needs of this challenging patient population. Addressing psycho-social and quality of life aspects may help increase completion rates of this often life-saving treatment. Overall survival appears to be poor after PDCRT. Advising a patient that reaching at least 50 Gy could offer a better chance for survival could prove vital.

Phase II trial of SM 88 in non-metastatic biochemical recurrent prostate cancer.

175 Background: Despite toxicity and no clear survival benefit, non-metastatic recurrent prostate cancer (nmPC) is typically treated with androgen deprivation therapy (ADT). SM88 is a relatively non-toxic novel combination therapy (amino acid analogue, CYP3a4 inducer, mTOR inhibitor and catalyst) based on the Warburg effect, with activity in a variety of cancers including prostate (JCO 2017 35, e16567). Phase I and II results demonstrated stable or rising testosterone levels while achieving a reduction of CTCs (circulating tumor cells) and no radiographic progression events (Annal Oncol 2017, 28(5):274-5). We now report results for toxicities typically seen with ADT. Methods: Prospective ongoing Phase Ib/II of SM88 (230mg po bid) in recurrent nmPC with rising PSA (PCWG3 definition), detectable CTCs, and no radiographically identified metastases at baseline. Results: Since Sept 2016, there have been 17 consented (of 34 planned) with 10 evaluable (completed &gt; 1 cycle) (median 7, range 1-13). Mean age was 71.2 (53-84); all had prior ADT after curative intent RT (50%) or surgery (50%); with no patient currently on ADT. Mean testosterone level was 307.6 ng/dL before SM88 and 349.2 after (p = 0.07, one-tail T test), rising in (5/10) or remained stable except for one patient who entered the trial castrate ( &lt; 2.5). Overall 70% had some grade 1-2 adverse event (AE) but no drug related serious AE. EORTC-QLQ-C30 relating to mental function domain (Q20-28) and QLQ-PR25 intimacy domains (Q44-50) remained stable, including 9 (90%) reporting no or resolved hot flashes; 7 (70%) reporting an improved or stable “interest in sex”; and 6 (60%) having “excellent” “overall health” and “QOL”. Weight and osteoporosis (measured by Urinary NTX) did not worsen; mean EKG QTc (422 ms); mean arterial pressure (95.1 mmHg); glucose (115.2 mg/dl) and hematocrit (41.5%) were not affected. Conclusions: Toxicities typically associated with ADT were not seen with SM88, a novel non-hormonal anti-neoplastic. Despite the limited follow-up, these data suggest that ADT may be avoided or delayed without progression in selected patients with nmPC. A phase III RCT of SM88 vs patient choice of hormonal or active surveillance is planned for confirmation of these results. Clinical trial information: NCT02796898.