RT Field Research Articles

Are All Colorectal Oligometastases Equal?

Stereotactic ablative body radiotherapy (SBRT) is offered to patients who have oligometastatic (OM) disease and are not suitable for surgical treatments. OM Colorectal (CRC) cancer has been identified as potentially having worse outcomes compared to other histology types. We hypothesize that tumor biology impacts outcome in OM CRC. A single institution of prospectively CRC patients treated with SBRT. Patients had <3 mets, in <2 organs on multimodality imaging and exhausted local treatments options. The PS 0-1 SBRT was delivered in 3-8 fractions depending on location. The α/β = 10 was used to estimate biological dose. Location of primary and KRAS status was recorded. Progression was defined by imaging criteria as local (within field), locoregional (same organ but outside RT field) or distant. Univariate analysis was performed with log rank tests of Kaplan-Meier curves and cox proportional hazard models. Significant variables on univariate testing were entered into a multivariate cox proportional hazard model. Between 05/2013 and 11/2017, 53 CRC metastases cases were treated and 40 patients had adequate data. Eighteen (45%) synchronous, 32 pts had ≥1 line of chemo. The median age was 68.5 years (range 36-89). Twenty-four patients were male. Primary site of disease was rectum in 18 (45%), left colon in 15 (37.5%) and right colon in 6 (15%). OM sites treated: 16 liver, 15 nodes, 6 lung, and 3 bone. Median BED10 was 100 Gy (range 48 – 151.2). Median follow up was 14 months (range 2 - 43). In-field local control at 1 year was 83.5% (95% C.I 69.4 – 100). Median PFS for the cohort was 9 months (95% C.I 5.8 – 15.2). The median PFS for the liver, lung and node metastases were 5, 13, and 19 months respectively. There was a significant difference in PFS based on metastasis location, with lymph node disease being associated with improved PFS (HR 0.25, 95% C.I 0.09 – 0.69, p = 0.007; overall log rank, p = 0.02). KRAS status was available for 22 patients (55%), 13 wild type and 9 mutant, with the remainder untested. WT KRAS status was associated with improved PFS (HR 0.29, 95% C.I 0.09 – 0.9, p = 0.037). No significant difference in PFS was seen when comparing groups by primary site, colon side, age, gender, or whether presentation was with synchronous or metastatic disease. On MVA, metastasis location of lung and lymph node and KRAS WT or unknown status, remain statistically significant predictors of improved PFS. In this small cohort, lymph node metastases are associated with improved PFS compared to lung, bone or liver sites independent of KRAS status. KRAS WT is an independent predictor of progression free survival for treatment with SABR. These findings could be used to further refine the selection of CRC OM for treatment with SABR and incorporating systemic treatment. The excellent local control, regardless of KRAS subtype, suggests that OM PFS is driven by locoregional or widespread failure highlighting need for exploring biological differences.

Multi-institutional report on toxicities of concurrent nivolumab and radiation therapy

PurposeRadiation therapy (RT) and nivolumab are standard therapies for a wide range of advanced and metastatic cancers, yet little is known about the toxicity profile of their combined treatment. The rate of grade ≥3 toxicities from nivolumab monotherapy and radiation-only palliative treatments has been reported at 10% to 18% and 0% to 26%, respectively. We reviewed our experience to assess the acute toxicity profile of concurrent RT-nivolumab. Methods and materialsA retrospective review of all consecutive patients from January 2015 to May 2017 who received concurrent RT-nivolumab was conducted at 4 separate centers. Concurrent RT-nivolumab was defined as RT completed between 3 days prior to initial nivolumab infusion and 28 days after the last nivolumab infusion. ResultsOf the 261 patients who received nivolumab, 46 (17.6%) had concurrent RT to 67 treatment sites. The median follow-up was 3.3 months (interquartile range, 1.7-6.1 months) and the 1-year overall survival rate was 22%. For the 11 of 46 patients (24%) who were alive at last analysis, the median follow-up was 12.8 months (interquartile range, 8.3-14.9 months). The most common histology, RT prescription, and treatment site were non-small cell lung cancer (23 of 46 patients; 50%), 30 Gy in 10 fractions (24 of 67 patients; 35.8%), and abdomen/pelvis (16 of 67 patients; 24%), respectively. Four patients with melanoma had concurrent ipilimumab and were removed from the final toxicity analysis of RT-nivolumab. Within 3 months of treatment with RT-nivolumab, 4 of 42 patients (9.5%) experienced grade 3 toxicity and 2 of these patients' toxicities were attributed specifically to the addition of RT: grade 3 hearing loss after whole brain RT and grade 3 pancreatitis after stereotactic body RT to the left adrenal gland. One death from transaminitis was attributed to nivolumab alone because the RT field did not encompass the liver. ConclusionsConcurrent RT-nivolumab did not appear to increase the toxicity profile from the previously reported toxicity rates from nivolumab or radiation alone.

A single-arm, phase II study assessing the efficacy of pembrolizumab (pembro) plus radiotherapy (RT) in metastatic triple negative breast cancer (mTNBC).

14 Background: Overall response rates of 13-19% have been reported with checkpoint inhibitor monotherapy in chemotherapy-resistant, PD-L1-positive mTNBC. RT is frequently used to enhance local control in mTNBC and has been reported to induce distant (abscopal) tumor responses when combined with immunotherapy. In this study, we evaluate the safety and efficacy of RT combined with a programmed cell death protein 1 (PD-1) inhibitor, pembro, in a single-arm, two-stage, phase II study in mTNBC. Methods: Eligible women had biopsy-proven mTNBC, ECOG performance status 0-2, and ≥2 measurable sites of metastatic disease with at least one site requiring RT. A total RT dose of 3000 cGy was delivered in 5 daily fractions. Pembro 200 mg was given intravenously within 3 days of first RT fraction, then every 3 weeks +/-3 days until disease progression. The primary endpoint was overall response rate at week 13 in the non-irradiated lesions by RECIST v1.1. Secondary endpoints included safety and overall survival. Tumor biopsies were obtained at baseline and at week 7. PD-L1 expression was not required for study entry. Results: Of the 17 women enrolled, the median age was 52 y (range 37-73y). and the median number of prior chemotherapies received for metastatic disease was 3 (range 0 to 8). Of the 8 women not evaluable at 13 weeks: 5 died secondary to disease-related complications (at weeks 2, 6, 7, 8, and 9) and 3 came off study due to disease progression prior to week 13. Of the 9 women evaluable at week 13, 3 (33%) had a partial response, 1 (11%) had stable disease and 5 (56%) had disease progression. The 3 partial responses represented 60%, 54%, and 34% decreases in tumor burden by RECIST v1.1 and were durable for 31, 21, and ongoing at 22 weeks, respectively. The stable disease response was durable for 22 weeks. Common toxicities were mild and included fatigue, myalgia and nausea. Conclusions: The combination of pembro and RT is well-tolerated. This is a poor prognosis population with 5/17 (29%) of patients dying within 12 weeks of study entry. However, durable responses were observed outside of the RT field in 3/9 (33%) patients who were unselected for PD-L1 expression and evaluable at 13 weeks. Clinical trial information: NCT02730130.

Prognostic factors of axillary lymph node-positive patients in clinical stage II and III breast cancer after neoadjuvant chemotherapy

Background: Surgery following neoadjuvant chemotherapy (NAC) is increasingly utilized for breast cancer treatment with respect to downstage and recurrent risk reduction. However, there are some uncertainties about the solutions of adjuvant radiotherapy (design of RT field and indication in low-risk patients) in patients after NAC, especially in clinically node-positive patients. The objective of this study is to identify the risk factors of loco-regional recurrence (LRR), relapse and overall survival (OS) regarding tumor response post-NAC in this institution. Methods: From 2007 to 2015, 90 patients with newly diagnosed clinical stage II (n=44) or III (n=46) breast cancer and pathological positive lymph nodes who received chemotherapy followed by breast conserving surgery or mastectomy, adjuvant radiotherapy, and some with adjuvant systemic therapy were identified. All of them received anthracycline-based or taxane-based chemotherapy, external beam radiotherapy and systemic treatment including target or hormone therapy if indicated. Methods: The patient characteristics included clinical T/N stage, pathologic T/N stage, response after NAC, tumor grade, surgical margin, the presence or absence of lymphovascular invasion and extracapsular extension, the total number of lymph nodes dissection, the positive lymph nodes ratio (pLNR), tumor biomarker status [estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER-2)], and adjuvant chemotherapy/target therapy or not. Univariate and multivariate analyses for risks of loco-regional recurrence (LRR), relapse (any local, regional or distant recurrence), and overall survival (OS) and the survival curves of LRR and relapse were performed. Results: After a median follow-up duration of 62 months (7–125 months), the multivariate analysis for risks of LRR showed that the status of clinical lymph nodes (cN2: HR =6.07, P=0.046; cN3: HR =30.22, P=0.001), response subgroups (stable disease: HR =3.01, P=0.047; progressive disease: HR =10.76, P&lt;0.001), and pLNR (67–100%: HR =4.32, P=0.025) have statistical significance. The multivariate analysis for risks of relapse also showed that the status of clinical lymph nodes (cN1 micro/N1: HR =3.97, P=0.037; cN2: HR =4.06, P=0.053; cN3: HR =10.39, P=0.005), response subgroups (progressive disease: HR =3.73, P=0.008) and pLNR (67–100%: HR =3.02, P=0.032) have statistical significance. The multivariate analysis of OS only showed the tumor biomarker status of triple-negative breast cancer (TNBC) (HR =3.04, P=0.048) has statistical significance. Conclusions: In this study, we recorded poor therapeutic response, advanced clinically positive lymph nodes, and higher proportional positivity of dissected lymph nodes showing poor outcome regarding the loco-regional control and relapse-free survival among patients with positive axillary lymph nodes after NAC.

Exploring the Usefulness of Concurrent Chemoradiation for Bulky Disease in the Setting of Advanced/Inoperable or Metastatic Breast Cancer

Improvements in systemic therapy (ST) have improved survival for breast cancer (BC) patients with locally advanced/inoperable and metastatic disease. Therefore, traditional palliative radiotherapy courses (e.g. 30 Gy/10 fractions) may not be sufficient treatment to secure durable control of bulky locoregional or symptomatic metastases and more aggressive approaches may be warranted. We sought to characterize the outcome of treating this population with concurrent chemoradiotherapy (CRT). We queried our institution's pharmacy database for BC patients treated with capecitabine (C) from 2012-2016 to identity patients that received CRT. Demographic, disease characteristics, treatment information and outcome was collected. Local failures (LF) were classified as progression documented within the irradiated field. All other failures were classified as distant failures (DF). Competing risks analysis was performed to estimate LF/DF. We used the linear quadratic formalism to calculate the biologically effective dose of the different RT regimens assuming α/β=3 (BED3). We chose to assess differences in LF using a cutoff value BED=80 Gy3 (equivalent to common whole breast RT regimens). Of 323 patients in the C database, 33 patients underwent 35 courses of CRT. 48% were ER+/PR+, 45% triple-negative, and 18% HER2+. For CRT, C (500 mg-1500 mg PO BID, was most commonly used (N=26); 7 patients received Carboplatin (AUC=2 IV weekly) or Cisplatinum (22.5-30 mg/m2 IV weekly); 1 patient received doxorubicin-liposomal 32mg/m2 IV q3 weeks; 1 patient received gemcitabine 300mg/m2 IV weekly. At the time of CRT, 4 pts had inoperable disease, 11 pts had local-regional recurrence (LRR), and 18 patients had distant metastatic disease (DM). The median number of prior lines of ST was 4 (range, 1-11) for DM patients and 1 (1-4) for inoperable/LRR patients. Median PTV was 886 cc (range, 180-2956 cc) for inoperable/LRR and 427 cc (34-3336 cc) for DM. 28% were treated with ≤2Gy/fraction to a median dose of 60 Gy (range, 36-66 Gy); 46% were treated at 2.5-3Gy/fraction to a median dose of 45 Gy (30-60 Gy); and 26% were treated at >3Gy/fraction to a median dose of 48 Gy (22.8-68 Gy). Median follow-up was 8 months. The 1-year LF was 23%, DF 71%, and OS rate 54%. Patients that received BED3≥80 Gy vs. <80 Gy had numerically lower rates of LF at 1 year (18% vs. 39%, p=0.09). Grade 3 acute toxicity was low (9% Grade dermatitis; 9% hematologic). Patients resumed standard dose ST at a median of 10.5 days after completion of CRT. We found that CRT for bulky disease in the breast, nodal or metastatic sites is well-tolerated in heavily pre-treated BC patients. Patients returned promptly to ST and at 1 year an overall local control of 77% was achieved, and 82% when an RT regimen with BED>80 Gy3 was used. The predominant failure pattern was at distant sites outside the RT field. We suggest that this approach warrants future prospective studies and hypofractionated regimens with a BED>80 Gy3 is recommended.

Outcomes of a Large Single Institutional Series of Radiation Associated Sarcomas

Radiation associated sarcoma (RAS) is a rare complication from radiation therapy. We investigated the clinicopathological characteristics, treatment strategies, and oncologic outcomes of these patients. An institutional review board approved institutional database of 12,961 primary bone or soft tissue sarcomas (1960-2016) was queried to find sarcomas arising within prior RT field of distinct prior malignancies at least 1 year after completion. Cases meeting criteria were further analyzed. Two hundred twenty-nine RAS were identified, representing 1.77% of sarcomas seen at our institution. Features of prior malignancies included: breast cancer (23.2%), Hodgkin lymphoma (11.8%), prostate (5.9%), cervical SCC (4.9%), non-Hodgkin lymphoma (4.4%), retinoblastoma (3.9%), colorectal (3.5%), ALL (3.0%), neuroblastoma (4, 2.0%), embryonal rhabdomyosarcoma (2.0%), Ewing sarcoma (1.5%), and medulloblastoma (1%); 2 had Li Fraumeni’s syndrome. Prior malignancies were treated with RT (median 55 Gy, 10-79.2 Gy); 46% had chemotherapy. Median age at prior malignancy was 49.5 years (2 mo-87 years) and for RAS was 60 years (10-93 years). Median interval from prior malignancy to RAS was 11 years (1-50 years). Features of RAS included: female (57.1%), male (42.9%), soft tissue (70.4%), bone (29.65), trunk (63.1%), head/neck (19.2%), extremity (17.7%), abdomen (14.4%), spine/bony pelvis (13.5%), and others; histologies osteosarcoma (27.6%), angiosarcoma (18.2%), fibrosarcoma (9.9%), UPS/MFH (9.9%), leiomyosarcoma (5.9%), MPNST (4.9%), and others (23.6%); median size 7.5 cm (1-25 cm), grades 1 (635), 2 (635), and 3 (48.8%). 77.8% were M0. Treatment of RAS consisted of surgery only (48%), surgery + RT (43.3%), RT only (7.4%), or neither (1.3%); 42.4% had chemotherapy. On Cox multivariate analysis, age (P < 0.001) and size >5 cm (P = 0.001) predicted worse OS whereas surgery predicted better OS (HR = 0.486, P = 0.002). Radiation associated (RA)-MPNST has worse CSS survival (HR = 2.51, P = 0.03), whereas RA-UPS/MFH predicted better CSS (HR = 0.36, P = 0.039) versus RA-osteosarcoma, angiosarcoma, fibrosarcoma, or leiomyosarcoma. Head/neck RAS (HR = 0.37, P = 0.017) and size 5-8 cm (HR = 2.2, P = 0.013) predicted worse LC. Size 5 to 8 cm (HR = 2.6, P = 0.012) also predicted lower DMFS. Of 158 M0 patients (median follow-up 33.4 mo., 1-548.7 mo.), 5 year OS was 41.8%, CSS, 53.8%, LC 53.7%, and DMFS 60.3%. Increasing age (P = 0.018) and RA-MPNST (HR = 3.60, P = 0.015) had worse OS5 versus spontaneous bone and soft tissue sarcomas (HR = 2.67, P < 0.01) and CSS (HR = 3.32, P < 0.01) independent of other factors. RAS have worse outcomes than spontaneous bone and soft tissue sarcomas with variability across histologies, size, age, and sites. Further understanding of clinical and biological differences/similarities across and between RAS vs. spontaneous sarcomas may improve treatment strategies.

247P - A single-arm, phase ii study assessing the efficacy of pembrolizumab (pembro) plus radiotherapy (RT) in metastatic triple negative breast cancer (mTNBC)

Background: Overall response rates of 13-19% have been reported with checkpoint inhibitor monotherapy in chemotherapy-resistant, PD-L1-positive mTNBC. RT is frequently used to enhance local control in mTNBC and has been reported to induce distant (abscopal) tumor responses when combined with immunotherapy. In this study we evaluate the safety and efficacy of RT combined with the anti-PD-1 inhibitor, pembro, in a single-arm, two-stage, phase II study in mTNBC (NCT02730130). Methods: Eligible women had biopsy-proven mTNBC, ECOG performance status 0-2, and ≥2 measurable sites of metastatic disease with at least 1 site requiring RT. A total RT dose of 3000 cGy was delivered in 5 daily fractions. IV pembro was given at 200mg within 3 days of first RT fraction then every 3 weeks until disease progression. The primary endpoint was overall response rate at week 13 in the non-irradiated lesions by RECIST v1.1. Secondary endpoints included safety and overall survival. Tumor biopsies were obtained at baseline and at week 7. PD-L1 expression was not required for study entry. Results: As of May 1, 2017, the study has completed enrollment (N = 17) with 4 women on treatment pending 13-week evaluation. Median age was 52y (range 37-73y). Median number of prior therapies received for metastatic disease was 3 (range 0 to 8). Of the 7 women not evaluable at 13 weeks: 5 died secondary to disease-related complications (at weeks 2, 6, 7, 8, and 9) and 2 came off study due to disease progression prior to week 13. Of the 6 women evaluable at week 13, 2 (33%) had a partial response (PR), 1 (17%) had stable disease (SD) and 3 (50%) had disease progression. The 2 PRs represented 76% and 75% decreases in tumor burden by RECIST v1.1 durable for 21 and 31 weeks, respectively. SD response was durable for 30 weeks. Common toxicities were mild and included fatigue, myalgia and nausea. Conclusions: The combination of pembro and RT was well-tolerated. This is a poor prognosis population with 5/13 (38%) evaluable patients dying within 12 weeks of study entry. However, durable responses were observed outside of the RT field in 2/6 (33%) patients who were unselected for PD-L1 expression and evaluable at 13 weeks. Safety and toxicity data for all study patients will be presented. Clinical trial identification: NCT02730130 Legal entity responsible for the study: Memorial Sloan Kettering Cancer Center Funding: Merck Disclosure: H.L. McArthur: Advisory boards for Celgene, Merck, OBI Pharma, Spectrum, Syndax, Roche, Peregrine, Calithera, Eli Lilly, and TapImmune. Research supported by Bristol-Myers Squibb; Eli Lilly; MedImmune, LLC/AstraZeneca; and Merck. C.A. Barker: In the past year has received research funding from Elekta, Merck, and Amgen; honoraria from Driver Group, a biotechnology company; and served as a Pfizer advisory board consultant. A. Gucalp: Research funding from Pfizer and Innocrin related to other work in triple negative breast cancer. A. Ho: Research funding by Merck. All other authors have declared no conflicts of interest.

High-dose palliative radiotherapy for malignant pleural mesothelioma.

High-dose radiotherapy to the hemithorax for patients with malignant pleural mesothelioma is a controversial treatment. Between 2003 and 2013 our institution had a policy of giving hemithoracic radiotherapy to at least 45Gy. This retrospective study reports survival, progression and toxicity associated with this policy. Seventy-one patients with pleural mesothelioma were irradiated with doses of 45-60Gy. Conformal radiotherapy (3D-CRT) to the lower hemithorax was used for 17 and intensity-modulated radiotherapy (IMRT) to the whole hemithorax for 54 patients. All patients have been followed up for at least 2years from commencement of radiotherapy. Sixty-four patients (90%) completed planned radiotherapy and seven stopped early, usually due to progressive disease. Median overall survival was 9.5months (95% CI: 7.7-12.4) and median progression-free survival was 4.9months (95% CI: 4.4-5.8). Eighty-seven per cent of patients progressed or died within 2years: 25% in-field, 49% outside the RT field and 13% died without progression. Severe toxicity (grade 3-5) was observed in 53% of 3D-CRT and 78% of IMRT patients, most commonly pulmonary fibrosis 27%, radiation dermatitis 18%, dyspnoea 11%, GGT increased 11%, pneumonitis 10%, pleuritic pain 8% and fatigue 8%. There were two, possibly three, treatment-related deaths. High-dose radiotherapy to the hemithorax caused significant toxicity to most patients with no improvement in survival. Lower doses of radiotherapy to limited volumes may be useful for palliative purposes.

Phase II clinical trial of first-line combination of radiation followed by gemcitabine, dexamethasone, and cisplatin (GDP) chemotherapy for early-stage extranodal natural killer/T-cell lymphoma with unfavorable prognostic factors: The GREEN study (NCT02276248).

7540 Background: Currently concomitant or sequential chemotherapy with radiotherapy has been recognized as the standard treatment for extranodal natural killer/T-cell lymphoma, nasal type (ENKTL). However, the optimal schedule has not been fully defined. Methods: We designed a phase II prospective study to investigate the efficacy and toxicity profile of sequential radiation followed by systemic GDP (gemcitabine, dexamethasone and cisplatin) chemotherapy on previously untreated early-staged (stage IE/IIE) ENKTL patients with at least one unfavorable prognostic factor. The primary endpoint was 2-year progression-free survival (PFS). Secondary endpoints were 2-year overall survival (OS), overall response rate (ORR), and toxicity. Results: A total of40 patients were enrolled and completed the entire course of treatment between June 2010 and June 2014. The median age was 38 (range 25-63) years old. All the enrolled patients presented with at least one unfavorable prognostic feature: age &gt; 60 years (5.0%), B symptom (40%), elevated serum LDH (40.0%), regional lymph node involvement (32.5%) and primary tumor invasion (87.5%). At the completion of the whole treatment, ORR was 97.5% and the complete remission rate was 95.0%. Median follow-up time was 43.7 months (range 9.4-72.3 months). 2-, 3-, 5-year PFS rates were 84.7%, 82.1%, 77.5%, and OS rates were 89.9%, 87.1%, 79.7%, respectively. Recurrence within the RT field was observed in four patients and systemic failure in three individuals. Grade 1-2 skin reaction and mucositis were the main toxicity related to radiation. Grade 3-4 neutropenia (12/40), thrombocytopenia (7/40) and anemia (2/40) were observed during GDP chemotherapy. No clinically significant late toxicities were observed during follow-up visits. Conclusions: The current results indicates that first-line radiation followed by GDP chemotherapy can be one of the most effective and feasible treatment schedule for early-stage ENKTL patients, especially those with poor prognostic factors. Clinical trial information: NCT02276248.

PUB057 Re-Irradiation of Non-Small Cell Lung Cell Cancer Recurrences with Stereotactic Body Radiotherapy

Decision of salvage therapy for lung cancer recurrences is a major problem because of poor results with re-treatments having greater risk of side-effects. Stereotactic body radiotherapy (SBRT) is a promising technique in re-irradiation of lung cancer recurrences. In this study, we intent to present our results, including the toxicity and outcome of our patients treated with SBRT after radiotherapy failure. 403 patients were treated with SBRT for lung cancer at our department between June 2010 and August 2015. Among these, we identified 16 patients who were re-irradiated using SBRT. PET-CT was used in staging in all patients. All patients had recurrent disease only within the previous radiotherapy treatment volume. The median previous EBRT dose was 66 Gy (range, 46 - 66 Gy). Tumor responses were evaluated with PET-CT 3 months after SBRT and with computerized tomography (CT) every 3 months interval. Outcomes analyzed were > grade 3 radiation pneumonitis, overall survival (OS), local control (LC), progression free survival (PFS) and distant metastasis. The median follow-up time was 30 months from salvage SBRT. The locations of recurrent tumors were central in 12 and peripheral in 4 patients. The median largest tumor size was 4.35 cm (range; 1.4 and 6.6 cm) and planning target volume was median 47.3 cm3 (range; 5.4 and 153.4 cm3). The median SBRT dose was 38 Gy (range; 30 – 60Gy). Total biological equivalent dose (BED) was 63 Gy10 (range, 48 - 115 Gy10) and SBRT was applied after a median time of 12 months (range; 3-36 months) from prior radiation. Complete response was in 13, partial response was in 2, stable or progressive disease was observed in 1 patient. The 1 year, 2 year and 3 year LC rate was 93.8%, 85.2% and 85.2% respectively. The 1 year, 2 year and 3 year OS rate was 87.5% - 67.3% and 40.4% respectively. One and 3-year PFS rates were 49.2% and 28.1% respectively. At the last follow-up 5 patients were alive with no evidence of disease and one patient was alive with systemic metastases. The rate of symptomatic > grade 3 pneumonitis was 12.5 % and one patient developed fatal pneumonitis. Symptomatic > grade 3 chest wall pain or esophagitis was not observed. Salvage therapy with re-irradiation with SBRT technique for in-field recurrent lung tumors appears to be a effective and well-tolerated option for cautiously selected patients even centrally located. Our results suggest that, lower BED doses could still provide excellent LC for recurrent lung tumors in the previous RT field with an acceptable complication rate.

Long term results and patterns of recurrence from SCOPE 1: A phase II/III randomised trial of definitive chemoradiotherapy (dCRT) plus or minus cetuximab (dCRT+C) in esophageal cancer.

118 Background: One of the largest trials in dCRT for localised oesophageal cancer, SCOPE 1 tested the role of adding cetuximab to conventional dCRT, and showed that this was associated with greater toxicity and worse survival. Here we present the long-term outcomes. Methods: Phase II/III trial. Randomisation: cisplatin 60mg/m2 D1 and capecitabine 625mg/m2 daily D1-21 for 4 cycles with/without Cetuximab 400mg/m2 D1 followed by 250mg/m2weekly. RT: 50Gy in 25 fractions given concurrent with cycles 3 and 4. Recruitment: Feb 2008 - Feb 2012, when the IDMC recommended trial closure on the basis of futility. Results: 258 patients (dCRT = 129; dCRT+C = 129) were recruited from 36 centres. Median follow-up (IQR): 46.7 (36.0-49.0) months for all surviving pts. 65.1% (dCRT arm) and 69.8% (dCRT+C arm) of patients had died. Esophageal cancer was the cause in 82.1% and 86.7% of deaths respectively (p = 0.41). Median OS months (95% CI) was 34.5 (24.7-42.3) in dCRT and 24.7 (18.6-31.3) in dCRT+C (HR 1.25, p = 0.137); corresponding 3-year OS (95% CI) was 47.2% (38.2%-55.7%) and 37.6% (29.1%-46.0%). Median PFS (95% CI): 24.1 (15.3-29.9) and 15.9 (10.7-20.8) months respectively (HR1.28, p = 0.114). There was some evidence that local PFS (within RT field) was lower in the dCRT+C arm (HR1.38, p = 0.051). On multivariable analysis including treatment arm, Stage I-II ds (vs Stage III), full-dose RT and higher cisplatin dose intensity ( ≥ 75% vs &lt; 75%) were associated with improved OS and PFS. Patterns of recurrence (n [%]) were similar in both arms (see table). In dCRT arm, 31/38 pts (81.6%) with local relapse within the RT field compared to 40/48 (83.3%) in the dCRT+C arm (p = 0.8). Conclusions: The mature analysis shows unprecedented survival in dCRT arm, comparable to surgical trials (e.g. 3-year OS % [95% CIs] in OE05: CF 39 [35, 44] and ECX 42 [37, 46], in OE02: 31 [27, 36]). OS inferiority of dCRT+C is no longer statistically significant. The lower PFS (within RT field) in the dCRT+C arm was consistent with the lower number of patients receiving full dose of RT in the dCRT+C arm. Clinical trial information: 47718479. [Table: see text]

How many patients could have a salvage local treatment after radiotherapy/brachytherapy for prostate cancer?

23 Background: In our institution, as soon as biochemical relapse (BR; nadir PSA + 2 ng/ml) occurred after external beam radiotherapy (EBRT) or brachytherapy (BT), 18-fluorocholine-PET-CT (18-FCH-PET) with or without multiparametric prostate MRI are performed. The aim is to select patients for a salvage local treatment (SLT) with a curative intent. We presented here the results of this approach. Methods: Records of patients with BR, without clinical evidence of relapsing disease and with at least a18-FCH-PET performed, were retrospectively reviewed. Patients were considered eligible for SLT if the relapse was only local or in case of nodal relapse reasonably encompass in a RT field. Results: Between 2010 and 2014, 89 pts were included, 23 initially treated with BT and 66 with EBRT. Prognostic group at diagnosis were: favourable: 25 (28%), intermediate: 35 (39%), unfavourable: 29 (33%). At the time of relapse, mean age was 72 yrs and mean PSA level: 6.2 ng/ml. After 18-FCH-PET ± MRI, patients were classified as: no target lesion identified: 20 (22.5%); local relapse: 35 (39%); nodal relapse: 22 (25%); distant metastases: 12 (13%.5%). Among 35 pts with a local relapse, 14 had SLT (cryotherapy:13; cyberknife:1). Reasons to not performed SLT were: advanced age or poor performance status: 10; Gleason 8-10: 2; T3 on MRI: 2; Patient refusal (fear of incontinence): 7. Among 22 pts with a nodal relapse, only 3 could have salvage EBRT. Reasons to not performed SLT were: old age or poor PS: 5; extensive nodal relapse: 8; local and nodal relapse: 6. At the end, 57 pts (64%) are potentially eligible for SLT and 17 (19%) could have it. Conclusions: In routine practice, in a population of 89 pts with a BR, 64% are eligible for SLT but 19% could have it. Main reasons for not having SLT were absence of target lesions, extensive disease, or advanced age. This result justified the realisation of an extensive staging at the time of BR after EBRT or brachytherapy.

Concurrent Chemoradiation Therapy Followed by Consolidation Chemotherapy for Localized Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

To evaluate the effectiveness of concurrent chemoradiation therapy (CCRT) with 40 Gy followed by consolidation chemotherapy for localized extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type. From August 2004 to August 2012, 62 patients with newly diagnosed stage IE to IIE ENKTL underwent CCRT followed by consolidation chemotherapy. The median RT dose was 40 Gy. Cisplatin, 30 mg/m(2), was administered weekly during the RT course. Responders to CCRT were encouraged to undergo consolidation chemotherapy. Three different consolidation chemotherapy regimens were used consecutively: VIPD (etoposide, ifosfamide, cisplatin, and dexamethasone); VIDL (etoposide, ifosfamide, and dexamethasone followed by intramuscular injection of l-asparaginase); and MIDLE (methotrexate, etoposide, ifosfamide, mesna, and l-asparaginase). The median follow-up period was 49 months (range 8-112). After completion of CCRT, 56 patients (90.3%) had a complete response, 4 (6.4%) had a partial response, 1 (1.6%) had stable disease, and 1 patient (1.6%) had progressive disease (PD). Consolidation chemotherapy was recommended to 61 patients, after excluding the patient with PD, but was actually delivered to 58. Of these 58 patients, 56 (96.5%) had a complete response and 2 (3.5%) had PD. During the follow-up period, 17 patients (including 3 with PD) experienced progression. The median interval to progression was 11 months (range 1-61). Local failure developed in 6 patients, of whom, 2 had developed progression outside the RT field. For all patients, the 3-year overall survival, progression-free survival, and local control rates were 83.1%, 77.1%, and 92.4%, respectively. Grade ≥3 nonhematologic toxicity developed in only 3 patients (4.8%). Excellent clinical outcomes were achieved using CCRT with 40 Gy followed by consolidation chemotherapy. Additional investigation, however, is warranted to confirm our findings.

Active Breathing Control (ABC) Reduces Dose to the Heart and Preserves Local Control in Patients with Left Breast Cancer: First Report of a Prospective Trial with 8-Year Follow-up

Active Breathing Control (ABC) Reduces Dose to the Heart and Preserves Local Control in Patients with Left Breast Cancer: First Report of a Prospective Trial with 8-Year Follow-up

Breathing Adapted Radiation Therapy in Hodgkin Lymphoma: Do We Need the Staging PET/CT in Deep Inspiration Breath Hold?

was confirmed by PET (60%) or gallium (40%) in all patients. The median dose of consolidation RT was 24 Gy (range, 18-36 Gy). Four patients developed recurrent HL, two of which were in-field recurrences. Five and 10-year relapse-free survival were 95% (95% CI 0.87-0.98) and 93% (CI 0.82-0.97), respectively. Five and 10-year overall survival were both 98% (CI 0.92-0.99). The most common late effect was hypothyroidism which developed in 18 patients (20%). Seven secondary malignancies were diagnosed (2 basal cell carcinomas, 2 non-Hodgkin lymphomas, colon cancer, acute myelogenous leukemia, and small cell lung cancer). Only the lung cancer was within the RT field, diagnosed in an active smoker 13 years after treatment. One patient developed mild diastolic dysfunction; no other cardiac complications were diagnosed. Conclusions: Lower doses of RT may be sufficient when combined with >4 cycles of ABVD for UF HL. This strategy may decrease the risk of long-term complications. The standard approach of 4 cycles of ABVD and 30 Gy of RT should be compared to 6 cycles of ABVD and 20 Gy of RT. Author Disclosure: J. Torok: None. L.R. Prosnitz: None. M. Palta: None. Y. Wu: None. A. Beaven: None. L. Diehl: None. C.R. Kelsey: None.

Toxicity and Local Control With Intensity Modulated Radiation Therapy (IMRT) Using a Simultaneous Integrated Boost (SIB) Hypofractionated Approach for Non-Small Cell Lung Cancer (NSCLC)

Toxicity and Local Control With Intensity Modulated Radiation Therapy (IMRT) Using a Simultaneous Integrated Boost (SIB) Hypofractionated Approach for Non-Small Cell Lung Cancer (NSCLC)

Using Apparent Diffusion Coefficient to Predict Outcome of Preoperative Chemoradiation Therapy for Locally-Advanced Rectal Carcinoma

Conclusions: There is much uncertainty in the localization of the inferior edge of rectal tumors. Preoperative RT is known to cause fecal incontinence, sexual dysfunction, and hypogonadism. These toxicities might be minimized by more accurate delineation of inferior tumor extent. Based on these findings we are initiating efforts to endoscopically delineate inferior tumor extent with metallic markers at the time of staging ultrasound to more precisely guide RT field design. Author Disclosure: A. Wojcieszynski: None. M.A. Ritter: None. P.R. Pfau: None. T.J. Kruser: None.

Abstract C31: Downregulation of IL-12 through IL-6 production increased cancer metastasis after radiotherapy

Abstract Radiotherapy (RT) is a potent antitumor modality. However, unwanted effect is also reported such as increased metastasis through complex molecular mechanism including cytokines. Cytokines are soluble messengers that directly stimulate immune cells and stromal cells at the tumor site and enhance cancer cells recognition by immune cells. Numerous studies have investigated that cytokines have anti-tumor efficacy for cancer therapy. In this study, we investigated levels of 6 cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12 and TNF-α) in serum of before and after RT of HCC patients treated with RT and evaluate its significance in relation to clinical outcome. As a result, intrahepatic metastasis out of RT field increased in patients with IL-12 decreas after RT (p = 0.043). IL-12 is an inflammatory cytokine that induces interferon-γ production from Th1 and NK cells. IL-12 mainly produced from antigen presenting cells as dendritic cells (DCs) which against many tumors is probably the result of its stimulatory effects on cell mediated immune responses. Therefore, we investigated anti-tumor and anti-metastatic effects of mesenchymal stem cells expressing IL-12 (MSC/IL-12) treatment with ionizing radiation (IR) in murine hepatic cancer (HCa-1) model. Tumor bearing syngenic mice were treated with IR, MSC/IL-12 or combination of both. Combination of MSC/IL-12 and IR resulted in suppression of lung metastasis as well as significantly growth delay of Hca-1. Especially, expressions of CD4, CD8 and CD11C were increased in tumors of MSC/IL-12 and IR treated group compared with only IR. Also, to understand the detailed mechanism on anti-tumor effect of IL-12 in IR treated HCC, splenocyte were irradiated with 2, 5 Gy and measured IL-6 and IL-12 by ELISA after cultured. As results, IL-6 significantly increased by IR, while IL-12 increased at 1 day but it was decreased in dose dependent manner at 3days. These results indicated that IL-12 production could be mediated by IL-6 signaling. To prove that, DCs were irradiated with 5 and 10 Gy in presence or absence of LPS after differentiated from mice bone marrow and analyzed expressions of CD80 and 86 by FACS. The expression of CD80 and 86 decreased in irradiated-DCs comparing to no-irradiated DCs. Also, LPS-induced expressions of CD 80, 86 and IL-12 increased in α-IL-6 treated DCs compared with no-treated DCs. Taken together, diminishing IL-12 via IL-6 production by IR seems to increase the treatment failure after radiotherapy in hepatocellular carcinoma. Citation Format: Jinsil Seong, Eun Jung Lee, Keun Young Jeong. Downregulation of IL-12 through IL-6 production increased cancer metastasis after radiotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C31.

The efficacy of oral glutamine in prevention of acute radiotherapy-induced esophagitis in patients with lung cancer

Aim of the studyThis study explores the efficacy of oral glutamine in the prevention of acute radiotherapy-induced esophagitis in patients with lung cancer who are treated with thoracic radiotherapy.Material and methodsThis study was planned as a retrospective randomized experimental study. Forty-six patients with lung cancer, who were treated and kept under control between January 2008 and January 2010, were included in the study by the Department of Radiation Oncology, Faculty of Medicine, Dicle University. The patients were divided into two groups. The first group (n = 21) was given prophylactic oral powder glutamine (daily 30 g), while the second group (n = 25) was not given oral glutamine.ResultsThere were 21 patients in Group 1 (45.7%) and 25 patients in Group 2 (54.3%). No significant statistical difference was observed between the two groups in terms of age, gender, stage, histopathological type, treatment choice, received radiation doses, esophagus length in RT field, or location of the tumor (p > 0.05). A significant statistical difference was observed between the glutamine-supplemented group (first group) and the glutamine-free group (second group) according to the grade of esophagitis (p < 0.0001).ConclusionsIn our retrospective randomized experimental study, we determined that the severity of acute radiotherapy-induced esophagitis might be decreased with oral glutamine in patients with lung cancer who were treated with thoracic radiotherapy.

Abstract P4-15-03: Patterns of relapse following re-irradiation of the breast using partial breast brachytherapy (PBB)

Abstract Purpose: This study is undertaken to evaluate the patterns of relapse among patients with a prior history of irradiation where the RT field included the breast, and who received re-irradiation using PBB for a localized second cancer event in the breast using partial breast. Materials and Methods: Twenty-seven patients were enrolled in an IRB approved study. Nineteen patients had prior history of breast cancer treated with lumpectomy and external beam therapy (ERT), and 8 patients had prior history of mantle RT. All patients underwent lumpectomy with negative margins and received a median dose of 45Gy PBB. The median time interval between the primary breast cancer diagnosis and the second cancer event in the ipsilateral breast is 94-months (range 28-months to 211-months). The median time between mantle RT and the breast cancer is 245 months. Results: At a median follow up of 73 months following lumpectomy and PBB 14.8 % (4/27) patients developed a local recurrence and were salvaged by mastectomy. The 5-year Kaplan Meier local disease-free survival and mastectomy-free survival is 100% and 81%, respectively. Remarkably, one third of patients with prior history of mantle RT developed third primary cancers (pancreas, lung and renal). All patients with the third primary cancers died free of any relapse from the breast cancer. None of the patients with prior history of breast cancer developed a second malignancy, and 3/21 developed distant metastases. Conclusions: In appropriately selected patients with prior history of lumpectomy and ERT for breast cancer we observed a high rate of local control and freedom from mastectomy. Patterns of relapse among patients with prior mantle RT suggest that breast conservation and PBB was appropriate for treating early stage disease. Breast conservation therapy did not have a detrimental effect on breast cancer specific outcome and eventual patient survival. Patients motivated for breast conservation may have an alternative to mastectomy at initial diagnosis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-15-03.