Local-regional Failure Research Articles

Radiation-Induced Viral Activation in HPV-Associated Squamous Cell Carcinoma of the Oropharynx: A Prospective Analysis of Viral Expression in Saliva During Radiation Therapy

distant metastasis-free survival (DMFS) were comparable between both treatment arms (HR: OS Z 1.05, 95% CI Z 0.44-2.53, p Z 0.915; DFS Z 0.77, 95% CI Z 0.44-1.35, p Z 0.362; DMFS Z 0.81, 95% CI Z 0.39-1.71, p Z 0.585). One hundred twelve patients had EBV DNA analysis pre-treatment (N Z 56, GCP and control). Of this group of patients, 37 (66.1%) and 41 (73.2%) in the control and GCP arms, respectively, had detectable levels of EBV DNA pre-treatment. For patients with detectable EBV DNA levels, induction GCP seems to confer a favorable DFS and DMFS (HR: DFS Z 0.39, 95% CI Z 0.141.11, p Z 0.056; DMFS Z 0.45, 95% CI Z 0.13-1.49, p Z 0.166). In contrast, DFS and DMFS were comparable between both treatment arms in patients with undetectable EBV DNA levels at baseline (HR: DFS Z 0.74, 95% CI Z 0.18-2.97, p Z 0.617; DMFS Z 0.80, 95% CI Z 0.115.69, p Z 0.864). Local regional failure rates were comparable between both arms, independent of baseline EBV DNA levels. Conclusions: The addition of induction chemotherapy to concurrent chemoradiation therapy in locally advanced NPC remains controversial. Nonetheless, patients with detectable EBV DNA levels pre-treatment appear to benefit from induction GCP, both in terms of DFS and DMFS. Baseline EBV DNA level potentially has a role as a predictive marker in stratifying patients with stage 3/4 NPC for induction chemotherapy. Author Disclosure: M. Chua: None. O. Whee Sze: None. J. Wee: None. Y. Soong: None. D. Lim: None. T. Tan: None.

Predictive Value of p16 Status on the Development of a Pathologic Complete Response (pCR) at Planned Neck Dissection After Cisplatin Based Chemoradiation - A Second Analysis of RTOG 0129

distant metastasis-free survival (DMFS) were comparable between both treatment arms (HR: OS Z 1.05, 95% CI Z 0.44-2.53, p Z 0.915; DFS Z 0.77, 95% CI Z 0.44-1.35, p Z 0.362; DMFS Z 0.81, 95% CI Z 0.39-1.71, p Z 0.585). One hundred twelve patients had EBV DNA analysis pre-treatment (N Z 56, GCP and control). Of this group of patients, 37 (66.1%) and 41 (73.2%) in the control and GCP arms, respectively, had detectable levels of EBV DNA pre-treatment. For patients with detectable EBV DNA levels, induction GCP seems to confer a favorable DFS and DMFS (HR: DFS Z 0.39, 95% CI Z 0.141.11, p Z 0.056; DMFS Z 0.45, 95% CI Z 0.13-1.49, p Z 0.166). In contrast, DFS and DMFS were comparable between both treatment arms in patients with undetectable EBV DNA levels at baseline (HR: DFS Z 0.74, 95% CI Z 0.18-2.97, p Z 0.617; DMFS Z 0.80, 95% CI Z 0.115.69, p Z 0.864). Local regional failure rates were comparable between both arms, independent of baseline EBV DNA levels. Conclusions: The addition of induction chemotherapy to concurrent chemoradiation therapy in locally advanced NPC remains controversial. Nonetheless, patients with detectable EBV DNA levels pre-treatment appear to benefit from induction GCP, both in terms of DFS and DMFS. Baseline EBV DNA level potentially has a role as a predictive marker in stratifying patients with stage 3/4 NPC for induction chemotherapy. Author Disclosure: M. Chua: None. O. Whee Sze: None. J. Wee: None. Y. Soong: None. D. Lim: None. T. Tan: None.

Vaginal Vault High-Dose-Rate Brachytherapy Alone as Adjuvant Treatment of Early-Stage Endometrial Cancer: A Retrospective Study on 119 Patients

(DSS). Age-adjusted Charlson Comorbidity Score (HR 1.2, p Z 0.003), LVSI (HR 3.1, p Z 0.003), and RT (HR 0.43, p Z 0.01) were retained in the multivariate model for OS. Conclusions: Adjuvant RT appears to reduce the risk of local-regional failure and improve OS in this cohort of patients with early stage Type II endometrial cancer. However, distant failure is a challenge for women with type II endometrial cancer. Further investigation into optimal adjuvant systemic therapy in these patients appears justified. Author Disclosure: S. Vance: None. N. Rasool: None. M. Mahan: None. M.A. Elshaikh: None.

Vaginal Dose and Patient Reported Sexual Adjustment With MR-Guided Brachytherapy for Cervical Cancer

Purpose/Objective(s): To assess the efficacy of simultaneous integrated or late course accelerated boost with EBRT to vaginal stump in intermediate risk cervical cancer patients after radical hysterectomy. Materials/Methods: Between October 2009 and January 2012, patients with intermediate risk cervical cancer who had undergone radical surgery for stage IB-IIB were enrolled in this study. Patients were delivered either simultaneous integrated boost intensive modulated radiotherapy (IMRT) / volumetric modulated arc therapy (VMAT) (arm-A) or late course accelerated boost with three dimensionalconformal radiotherapy (3D-CRT) after IMRT/VMAT to the pelvic (arm-B). Chemotherapy with paclitaxel + cisplatin (TP) or 5-Fu + cisplatin (FP) were given concomitantly. The clinical target volume 1 (CTV1) was delineated according to the consensus guidelines of CTV in postoperative treatment of endometrial and cervical cancer. The vaginal dump was delineated to be CTV2. The planning target volume, PTV1 and PTV2 were created by extending the CTV1 and CTV2, respectively, using a margin of 10 mm in the axial plane except in the front of the rectal, where the margin is 5 mm. All the plans were performed in the pinnacle treatment plan system (TPS). In arm-A, 50.4Gy/28f and 60.2Gy/28f were delivered to PTV1 and PTV2, respectively, with simultaneous integrated boost IMRT/VMAT technique. In arm-B, a dose of 50Gy/25f was delivered to the PTV1 with IMRT/VMAT technique; and then, 9Gy/3f was boosted to PTV2 with 3D-CRT. Progress-free survival (PFS), the rate of local-regional failure and distance recurrence were compared between two arms. Results: Overall, 80 patients were enrolled in this study (42 in arm-A, 38 in arm-B). Median follow-up was 37 months (15-49m) in arm A and 32 months (16-47m) in arm B. 3year PFS rates was 90.5% in arm-A and 92.1% in arm-B (pZ 0.78). 3 year rate of local-regional failure and distant metastasis were 2.38% vs. 0%, and 7.14% vs. 7.89%, respectively. Conclusions: Both simultaneous integrated boost IMRT/VMAT and late course accelerated boost with EBRT after IMRT/VMAT to the pelvic are feasible and effective to the intermediate risk cervical cancer patients after radical hysterectomy. Author Disclosure: X. Wang: None. Y. Shen: None. Y. Zhao: None. Z. Li: None. S. Bai: None. F. Xu: None.

A Retrospective Review of Patient Outcomes Following High-Dose-Rate Brachytherapy in the Treatment of Cervical Cancer

Purpose/Objective(s): To assess the efficacy of simultaneous integrated or late course accelerated boost with EBRT to vaginal stump in intermediate risk cervical cancer patients after radical hysterectomy. Materials/Methods: Between October 2009 and January 2012, patients with intermediate risk cervical cancer who had undergone radical surgery for stage IB-IIB were enrolled in this study. Patients were delivered either simultaneous integrated boost intensive modulated radiotherapy (IMRT) / volumetric modulated arc therapy (VMAT) (arm-A) or late course accelerated boost with three dimensionalconformal radiotherapy (3D-CRT) after IMRT/VMAT to the pelvic (arm-B). Chemotherapy with paclitaxel + cisplatin (TP) or 5-Fu + cisplatin (FP) were given concomitantly. The clinical target volume 1 (CTV1) was delineated according to the consensus guidelines of CTV in postoperative treatment of endometrial and cervical cancer. The vaginal dump was delineated to be CTV2. The planning target volume, PTV1 and PTV2 were created by extending the CTV1 and CTV2, respectively, using a margin of 10 mm in the axial plane except in the front of the rectal, where the margin is 5 mm. All the plans were performed in the pinnacle treatment plan system (TPS). In arm-A, 50.4Gy/28f and 60.2Gy/28f were delivered to PTV1 and PTV2, respectively, with simultaneous integrated boost IMRT/VMAT technique. In arm-B, a dose of 50Gy/25f was delivered to the PTV1 with IMRT/VMAT technique; and then, 9Gy/3f was boosted to PTV2 with 3D-CRT. Progress-free survival (PFS), the rate of local-regional failure and distance recurrence were compared between two arms. Results: Overall, 80 patients were enrolled in this study (42 in arm-A, 38 in arm-B). Median follow-up was 37 months (15-49m) in arm A and 32 months (16-47m) in arm B. 3year PFS rates was 90.5% in arm-A and 92.1% in arm-B (pZ 0.78). 3 year rate of local-regional failure and distant metastasis were 2.38% vs. 0%, and 7.14% vs. 7.89%, respectively. Conclusions: Both simultaneous integrated boost IMRT/VMAT and late course accelerated boost with EBRT after IMRT/VMAT to the pelvic are feasible and effective to the intermediate risk cervical cancer patients after radical hysterectomy. Author Disclosure: X. Wang: None. Y. Shen: None. Y. Zhao: None. Z. Li: None. S. Bai: None. F. Xu: None.

619PD - Interim Results of a Randomized Controlled Phase III Trial of Elective Nodal Irradiation Plus Erlotinib Combined with Chemotherapy for Esophageal Squamous Cell Carcinoma (Nct00686114)

ABSTRACT Aim: Concurrent chemoradiotherapy is the standard treatment for unresectable esophageal squamous cell carcinoma (SCC). This phase III trial was designed to determine whether the addition of elective nodal irradiation (ENI) and/or erlotinib to concurrent conventional chemoradiotherapy containing cisplatin/paclitaxel (CP) improved survival. Methods: This study was a 2x2 factorial design, with erlotinib and ENI as factors. Chinese patients with esophageal SCC were randomized to: (A) ENI/concurrent CP/erlotinib; (B) ENI/concurrent CP; (C) conventional-field irradiation (CFI)/concurrent CP/erlotinib; (D) CFI/concurrent CP. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival, local-regional failure rate, and toxicity. Interim analysis was planned when 100 deaths were observed. NCT00686114. Results: At the interim analysis, 195 patients were recruited and 104 death events occurred. Median follow-up was 18.7 months (95% CI, 12.5 to 24.8) for all patients and 23.9 months for patients alive at last contact. There were no significant interactions between the two factors of ENI and erlotinib. Median OS was 33.5 months for ENI-treated patients (A + B) versus 15.3 months for CFI-treated patients (C + D; HR, 0.62; 95% CI, 0.42 to 0.92; P = .02). Median OS was 20.0 months for erlotinib-treated patients (A + C) versus 17.8 months for control patients (B + D; HR, 0.85; 95% CI, 0.57 to 1.25; P = .37). Patients treated with ENI plus erlotinib (A) achieved a 2-year survival rate of 61.6% and a median survival of 40.2 months. Hematologic toxicities grade ≥3 were the most common adverse events. Erlotinib was associated with a higher rate of all-grade rash events. Conclusions: This interim analysis shows an obvious tread toward benefits from ENI, and the addition of erlotinib to ENI combined with concurrent chemotherapy further prolongs OS in patients with oesophageal SCC. However, the results with respect to the value of ENI or erlotinib alone were not decisive; final OS analysis is estimated for late 2015. Disclosure: All authors have declared no conflicts of interest.

Long-Term Follow-Up Results of Simultaneous Integrated or Late Course Accelerated Boost With EBRT to Vaginal Stump in Intermediate-Risk Cervical Cancer Patients After Radical Hysterectomy

Long-Term Follow-Up Results of Simultaneous Integrated or Late Course Accelerated Boost With EBRT to Vaginal Stump in Intermediate-Risk Cervical Cancer Patients After Radical Hysterectomy

Pattern of Failure in Surgically Treated Patients with Cervical Esophageal Squamous Cell Carcinoma.

The aim of this study was to analyze the pattern of failure in patients who have undergone surgical resection for cervical esophageal squamous cell carcinoma. Case series with chart review. University hospital. Sixty-two patients who had undergone surgical resection of cervical esophageal squamous cell carcinoma from January 2001 through April 2012. Sites of failure were documented. Twenty-nine patients had developed treatment failure. Of the 29 patients, 14, 13, and 14 had developed local failure, regional failure, and distant metastasis, respectively. Of the 13 regional failures, the images of 2 patients were lost. The other 11 regional failures included left lateral nodal disease at level II (n = 2), level III (n = 4), and level IV (n = 7); right lateral nodal disease at level II (n = 2), level III (n = 3), and level IV (n = 3); and level VI (n = 4). The overall 2-year local failure-free survival rate and regional failure-free survival rates were 79.6% and 58.6% (P = .04) for patients with stage II disease and 79.6% and 59.6% (P = .054) for patients with stage III disease, respectively. The pattern of failure of cervical esophageal squamous cell carcinoma is characterized by early locoregional failure, especially in patients with stage III disease.

Effectiveness and Toxicities of Intensity-Modulated Radiation Therapy for Patients with T4 Nasopharyngeal Carcinoma

ObjectiveTo evaluate the effectiveness and toxicities in T4 nasopharyngeal carcinoma (NPC) using intensity-modulated radiotherapy (IMRT) combined with chemotherapy.MethodsThis is a retrospective analysis of 81 patients treated with intensity-modulated radiotherapy (IMRT). All the primary tumors were attributed to T4 stage according to the AJCC2010 staging system. And the distribution of disease by N stage was N0 in 13.6%, N1 in 30.9%, N2 in 37%, and N3 in 18.5%. Cisplatin-based chemotherapy was offered to all patients. Radiotherapy-related toxicities were graded according to the Acute and the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group (RTOG) scoring criteria. Chemotherapy-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0. Prognostic factors were assessed by univariate analysis.ResultsWith a median follow-up of 37 months, 12 patients experienced local regional failure and total distant metastasis occurred in 18 patients, representing the major mode of failure. Ten patients died. Among them, 70% died of distant metastasis. The 3-year actuarial rates of local failure–free survival (LFFS), regional failure–free survival (RFFS), distant failure–free survival (DFFS), overall survival (OS), and progression–free survival (PFS) were 83.8%, 97.4%, 81.3%, 90%, and 69.7%, respectively. Acute and late toxicities were mild or moderate.ConclusionsIMRT provides excellent local-regional control for T4 NPC. Distant metastasis remains the major cause of treatment failure. Further explorations of the sequence and regimen of systemic therapy are needed in the future.

Patterns of local-regional failure after primary intensity modulated radiotherapy for nasopharyngeal carcinoma

BackgroundTo analyze patterns of local-regional failure after primary intensity modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC).MethodsA total of 370 non-metastatic NPC patients consecutively treated with IMRT (with or without chemotherapy) were analyzed. Radiotherapy was administered using a simultaneous integrated boost (SIB) technique at the total prescribed dose of 66-70.4Gy (2.0-2.2Gy per fraction). The location and extent of local-regional failures were transferred to the pretreatment planning computed tomography (CT) for dosimetric analysis. The dose of radiation received by Vrecur (volume of recurrence) was calculated and analyzed with dose-volume histogram (DVH). Failures were classified as: "in field" if 95% of Vrecur was within the 95% isodose, "marginal" if 20% to 95% of Vrecur was within the 95% isodose, or "outside" if less than 20% of Vrecur was inside the 95% isodose.ResultsWith a median follow up of 26 months, 25 local-regional failures were found in 18 patients. The 1- and 2-year actuarial local-regional control rates for all patients were 99.7% and 95.5% respectively. Among the 22 local–regional failures with available diagnostic images, 16 (64%) occurred within the 95% isodose lines and were considered in-field failures; 3 (12%) were marginal and 3 (12%) were outside-field failures.ConclusionsIntensity-modulated radiotherapy provides excellent local-regional control for NPC. In-field failures are the main patterns for local-regional recurrence. Reducing the coverage of critical adjacent tissues in CTV purposefully for potential subclinical diseases was worth of study. Great attention in all IMRT steps is necessary to reduce potential causes of marginal failures. More studies about radioresistance are needed to reduce in-field failures.

Patterns of Local-Regional Failure in Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer Cases: Implications for Postoperative Radiation Therapy Clinical Target Volume Design

To analyze patterns of local-regional failure (LRF) for completely resected stage IIIA(N2) non-small cell lung cancer (NSCLC) patients treated in our hospital and to propose a clinical target volume (CTV) for postoperative radiation therapy (PORT) in these patients. From 2005 to 2011, consecutive patients with pT1-3N2 NSCLC who underwent complete resection in our hospital but who did not receive PORT were identified. The patterns of first LRF were assessed and evaluated as to whether these areas would be encompassed by our proposed PORT CTV. With a median follow-up of 24 months, 173 of 250 patients (69.2%) experienced disease recurrence. Of the 54 patients with LRF as the first event, 48 (89%) had recurrence within the proposed PORT CTV, and 6 (11%) had failures occurring both within and outside the proposed CTV (all of which occurred in patients with right-lung cancer). Ninety-three percent of failure sites (104 of 112) would have been contained within the proposed PORT CTV. For left-sided lung cancer, the most common lymph node station failure site was 4R, followed by 7, 4L, 6, 10L, and 5. For right-sided lung cancer, the most common site was station 2R, followed by 10R, 4R, and 7. LRF following complete surgery was an important and potentially preventable pattern of failure in stage IIIA(N2) patients. Ipsilateral superior mediastinal recurrences dominated for right-sided tumors, whereas left-sided tumors frequently involved the bilateral superior mediastinum. Most of the LRF sites would have been covered by the proposed PORT CTV. A prospective investigation of patterns of failure after PORT (following our proposed CTV delineation guideline) is presently underway and will be reported in a separate analysis.

Optimizing a risk stratification for local-regional failure after radical cystectomy using the SWOG 8710 cohort.

297 Background: Trials of adjuvant radiation (RT) after radical cystectomy + pelvic node dissection (RC) are in development, but patient selection criteria have not been clearly identified. We evaluated a published model predicting the risk of local-regional failure (LF) by applying the model to a multi-center patient cohort. We also assessed the model’s ability to stratify overall survival (OS) and isolated distant metastases (DM). Methods: The original LF risk model was derived from 442 patients who had a RC +/- chemotherapy at the University of Pennsylvania (PENN). Analysis identified 3 subgroups with significantly different LF risk based on pathologic stage (pT) and number of nodes dissected (<10 vs ≥10). This risk rubric was then applied to 264 patients in the multi-center SWOG 8710 trial randomized to RC +/- neoadjuvant chemotherapy. SWOG patients differed significantly from PENN patients in mean age, pT stage, number of nodes removed, surgical margin status, and use of neoadjuvant chemotherapy. In both cohorts, LF was any pelvic failure detected before or within 3 months of DM. Secondary endpoints were OS and DM. Competing risk analysis was used. Results: The original risk stratification was not fully validated in the SWOG cohort. Regression analysis of the SWOG data found margin status was more predictive of LF than number of nodes dissected. A revised risk stratification model combining pT stage, margin status, and number of nodes removed identified 3 subgroups in both the SWOG and PENN cohorts with significantly different LF risks: low (≤pT2), intermediate (≥pT3 with negative margins AND ≥10 nodes removed), and high (≥pT3 with positive margins OR <10 nodes removed) with 5 year LF rates of 8%, 20%, and 41% in the SWOG group and 8%, 19%, and 41% in the PENN cohort. The 3 subgroups also differed significantly in OS within both cohorts with 5 year OS of 62%, 39%, and 7% for SWOG and 60%, 31%, and 10% for PENN. The model did not stratify with respect to isolated DM. Conclusions: The revised risk model combining pT stage, margin status, and number of nodes excised provides a simple rubric to stratify LF risk in two significantly different bladder cancer populations and may inform the design of adjuvant RT trials.

Chemoradiation (CRT) followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant CRT and surgery for locally advanced rectal cancer: Results of the Spanish GCR-3 randomized phase II trial after a median follow-up of 5 years.

383 Background: In locally advanced rectal cancer in contrast with the conventional approach the administration of chemotherapy prior to chemoradiation (CRT) and surgery allow most patients receive planned treatment with better toxicity profile without compromising the pCR and complete resection rates, as we previously demonstrated. (J Clin Oncol 28:859-865, 2010). We now report on the 5-year outcomes of this randomized trial. Methods: Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinoma selected by Magnetic Resonance +/- endorectal ultrasound, were randomly assigned to arm A—preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)—or arm B— four cycles of CAPOX followed by CRT and surgery. The following five-year outcomes were assessed: the cumulative incidence of local-regional (LRF) and distance failure (DF), disease-free (DFS) and overall (OS) using the Kaplan-Meier method. Results: Of 108 patients accrued, 52 were randomly assigned to arm A and 56 to arm B. According to intention-to-treat analysis with a median follow-up time of 69.5 months, the 5-years DFS rates were 64.3% (95% CI, 49% to 76%) in arm A and 60.7% (95 CI, 46% to 72%) in arm B (P=0.73). The 5-year cumulative incidences of local relapse were 1.9 % and 7.1% in A and B arms respectively (P= 0.36). No significant differences were detected for 5-year cumulative incidence of distant metastases (21.1% and 23.2%; P = 0.80) and 5-years overall survival (77.9% and 74.7%; P= 0.64). Conclusions: Both approaches yield similar 5-y outcomes. Because of the associated acute toxicity sparing and better compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy prior to CRT and surgery may well be the next step in phase III testing versus the standard strategy to capture meaningful differences in DFS.

Outcomes and xerostomia after postoperative radiotherapy for oral and oropharyngeal carcinoma

We compared outcomes and xerostomia grade after postoperative intensity-modulated radiation therapy (IMRT) and conventional radiotherapy (RT) in patients with oral and oropharyngeal carcinoma. Eighty-eight patients with oral cavity (n = 77) and oropharyngeal (n = 11) carcinoma underwent postoperative IMRT (n = 44) or conventional RT (n = 44). Outcomes, failure patterns, volume, doses, salivary gland V30, and xerostomia grade were evaluated. The median follow-up was 53 months (range, 48-58 months). The median interval from surgery to RT was 4 weeks (range, 3-6 weeks). Twenty-one patients (7 and 14 for the IMRT and conventional RT groups, respectively) experienced local-regional failure. For the IMRT group, all 7 local-regional failures occurred in the high-dose target volumes. For the conventional RT group, there were 12 in-field failures, 1 at the margin, and 1 out-of-field. Nine patients experienced distant failure (5 and 4 for the IMRT and conventional RT groups, respectively). The 4-year local-regional control, disease-free survival (DFS), overall survival (OS), and distant-metastasis rates for the IMRT and conventional RT groups were 84.1% versus 68.2% (p = .055), 68.2% versus 52.3% (p = .091), 70.5% versus 56.8% (p = .124), and 11.4% versus 9.1% (p = .927), respectively. Xerostomia grade after RT was lower for IMRT compared to conventional RT (p < .001). Postoperative IMRT for oral and oropharyngeal carcinoma significantly improves mean dose, salivary gland V30, and xerostomia grade when compared to conventional RT. The predominant failure pattern was local. No differences were found in survival outcomes between both groups. There was a marginal difference in local-regional control.

Toxicity and Survival After Reirradiation (reRT) With IMRT for Recurrent Squamous Cell Cancer of the Head and Neck (SCCHN): Management of Recurrent Head-and-Neck Squamous Cell Carcinoma

ReRT of the H&N with IMRT can achieve extended survival, but is associated with substantial toxicity and local-regional failure (LRF) is still common. We sought to identify predictors of toxicity and LRF after reRT to identify pts most likely to benefit from reRT.

Reliability of post-chemoradiotherapy F-18-FDG PET/CT for prediction of locoregional failure in human papillomavirus-associated oropharyngeal cancer

Although widely adopted, the accuracy of post-chemoradiotherapy (CRT) 18F-fluorodeoxygluocose positron emission tomography/computed tomography (PET/CT) for predicting locoregional failure (LRF) in human papillomavirus-related (HPV+) oropharyngeal cancer (OPC) remains poorly characterized. We assessed the predictive value of 3-month PET/CT response for LRF in this population. 101 consecutive patients with stage III-IV HPV+ OPC who underwent definitive CRT with pre-treatment and 3-month post-CRT PET/CT at our institution from 3/2005-3/2011 were included. 3-month PET/CT response was re-classified as complete-response (CR), near-CR, or incomplete-response (<CR) for each the primary site and neck. Accuracy of 3-month PET/CT for predicting local failure (LF) and regional failure (RF) was analyzed. Among 98 patients with an evaluable primary tumor, LF occurred in 2/67 patients with CR, 0/20 with near-CR, and 1/11 with <CR on 3-month PET/CT. Of 98 node-positive patients, RF occurred in 6/80 with CR, 2/9 with near-CR, and 0/7 with <CR in the neck at 3 months. Sensitivity and positive predictive value (PPV) of 3-month PET/CT response for LF and RF were low (0-33%), despite a high negative predictive value (NPV) (91-98%). SUVmax thresholds or % change did not improve the accuracy of 3-month PET/CT. Use of additional PET/CT surveillance after 3 months in 67 patients accurately detected both LF (96%) and RF (97%). In the largest study to-date of PET/CT response assessment in HPV+ OPC, 3-month PET/CT response demonstrated high NPV for LRF, though with disappointing sensitivity and PPV. Subsequent PET/CT surveillance showed potential utility for early detection of LRFs.

Factors associated with local-regional failure after definitive chemoradiation for locally advanced esophageal cancer.

Locally advanced esophageal cancer is often treated with a trimodality approach. While a substantial proportion of such patients initially achieve a clinical complete response (cCR) after chemoradiation, only a small proportion achieve durable control. We analyzed patients who reached cCR after definitive chemoradiation for esophageal cancer to identify clinical predictors of local disease recurrence. We identified 141 patients who obtained initial cCR after definitive chemoradiation without surgery for esophageal cancer from 2002 through 2009. The initial response to treatment was assessed by endoscopic evaluation and biopsy results, with cCR defined as having no evidence of disease present. Patterns of failure were categorized as in-field (within the planned treatment volume [PTV]), outside the radiation treatment field, or both. At a median follow-up of 22 months (range, 6-87 months), 77 patients (55 %) had experienced disease recurrence (local or both). Of first failures, 32 (23 %) were outside the radiation field, followed by 30 (21 %) within the field, and 15 (11 %) were both. By multivariate analysis, in-field failure after cCR was associated with a pretreatment standardized uptake value on positron emission tomography of >10 (subhazard ratio [SHR] 3.31, p = 0.023) and poorly differentiated tumors (SHR 3.69, p = 0.031). All failures, in-field and out-of-field, correlated with non-Caucasian ethnicity (SHR 2.55, p = 0.001), N1 disease (SHR 2.05, p = 0.034), T3/T4 disease (SHR 3.56, p = 0.011), and older age (SHR 0.96, p = 0.008). Our data suggest that selected clinical characteristics can be used to predict failure patterns after definitive chemoradiation. Such risk-assessment strategies can help individualize therapy.

EOutcomes-H&amp;N: Development of an electronic point-of-care outcomes collection system for head and neck cancer.

247 Background: Outcomes data increases the ability to understand the impact of cancer treatment and helps ensure that we direct appropriate investments to achieve improvements in quality of care. Cancer Care Ontario (CCO) has developed an outcomes data collection system for patients with head and neck cancer treated with radiotherapy. Methods: Clinicians involved in the care of these patients agreed on 5 key clinical outcomes to collect as a part of this initiative: local failure, regional failure, distant metastasis, second primaries, and treatment toxicity. Based on the Princess Margaret Hospital Head and Neck Cancer Anthology of Outcomes process, CCO has developed a similar system to collect outcomes data at the point-of-care on a provincial scale. The population-based provincial system aims to provide practice efficiencies and allow for evolution of the system in response to user feedback and expansion to other clinical areas. Results: The system includes a secure web application and iPad mobile application to facilitate the collection and management of outcomes data for head and neck cancer patients treated with radiotherapy in Ontario. Cancer centres upload patient clinic schedule details (including patient identifiers and appointment dates) prior to clinics. A list of patient summaries, including corresponding diagnosis, radiotherapy information and previously recorded outcomes is then generated. In clinic, physicians use these lists to capture outcomes noted at the point-of-care. Data captured are then transferred in real time to a secure central database. Following initial testing, the application was piloted to assess usability, system reliability, and overall satisfaction. Initial results show high physician satisfaction and no documented issues with system availability. Feedback has identified potential improvements and will inform future modifications. Conclusions: The identification of potential variation in recurrence, toxicity and survival data will inform the areas in which quality improvement initiatives or additional investments may be needed. The intent is to leverage project learnings for future outcomes initiatives in other diseases and treatment modalities.

Cetuximab plus radiotherapy in elderly patients with unresectable locally advanced squamous cell carcinoma of head and neck region

result of blood flow or nerve sensation loss secondary to surgery. All burns healed with appropriate treatment with long term radiation sequelae no worse than with standard radiation therapy alone. Conclusion: Hyperthermia is a safe and effective radiosensitizing modality of treatment for geriatric cancer patients at high risk for local-regional control failure. It is FDA approved, has excellent efficacy and safety, but unfortunately remains an underutilized modality of treatment.

Increasing Pretreatment Tumor SUVmean Is Associated With Local Regional Failure After Chemoradiation for Locally-Advanced Non-Small Cell Lung Cancer

Local regional failure (LRF) after definitive chemoradiation for stage IIIA and IIIB non-small cell lung cancer (NSCLC) remains high. The purpose of this study was to determine if pre-treatment [F-18] fluoro-D-glucose-positron emission tomography (FDG PET) parameters are associated with LRF after chemoradiation. This IRB-approved retrospective study analyzed patients with stage IIIA and IIIB NSCLC treated with definitive chemoradiation between the years of 2006 and 2011 at Emory University Hospital. Patient and treatment characteristics were collected from electronic charts. The SUVmean, SUVmax, and SUVpeak of the primary tumor and involved lymph nodes were extracted from the pre-treatment FDG PET CT by a single user. Locoregional failure was defined as failure within the ipsilateral lung, hilum or mediastinum. Multivariate analysis for factors associated with LRF was performed using the Cox proportional hazard method. SUV parameters were analyzed as continuous variables. Sixty-one patients were identified. Median follow-up was 19 months. Eighteen percent of patients were treated with Intensity Modulated Radiation therapy (IMRT), 10% with 3D and IMRT techniques, and 72% with 3D conformal technique. Thirty-nine percent of patients received daily on board imaging (OBI). Median total RT dose for all patients was 66 Gy. Concurrent chemotherapy was delivered to 90% of patients. The median pre-treatment SUVmax, SUVmean, and SUVpeak values were 15.2 (6.6-50.1), 4.52 (2.2-9.04), and 13.7 (4.85-44), respectively. A LRF occurred in 36% of patients. Median time to LRF was 11.4 months. On multivariate analysis, increasing pre-treatment tumor SUV mean was significantly associated with LRF (HR: 1.77; 95% CI, 1.18-2.65; p < 0.01). Lower T stage (HR: 0.04; 95% CI, 0.004-0.51; p = 0.013), lower N stage (HR 0.038, 95% CI, 0.004-0.34, p < 0.01) and white race (HR: 0.266; 95% CI, 0.076-0.931; p = 0.04) were associated with a decreased risk of LRF. Other factors, including radiation technique, use of OBI, SUVmax, and SUVpeak were not significantly associated with LRF on multivariate analysis. Pretreatment FDG PET tumor SUVmean is associated with LRF after chemoradiation for stage III NSCLC, and warrants further investigation.