Cumulative Incidence Of Locoregional Failure Research Articles

Competing Causes of Death and Medical Comorbidities among Patients With Human Papillomavirus-Positive Versus -Negative Oropharyngeal Carcinoma and Its Impact on Compliance to Radiation Therapy

differences in outcomes in LA-HNSCC between C225 and CDDP were influenced by HPV Status. Materials/Methods: We reviewed the records of 147 consecutive patients with LA-HNSCC treated with definitive chemo-RT at one of our 3 institutions with known HPV status. Patients with nasopharyngeal carcinoma, oral cavity carcinoma, or distant metastasis at time of presentation were excluded. Further, patients who received induction chemotherapy or additional concurrent systemic agents were excluded. At institution 1, HPV Status was determined by p16 or HPV ISH; at institute 2 by PCR or p16; and at institute 3 by p16 or non-keratinizing histology. Smoking status was divided between those with a 10 pack-yr history or greater vs those without. Actuarial curves were created with the Kaplan-Meier method and multivariate Analysis (MVA) was performed with a Cox-regression model. Results: Median follow-up in surviving patients was 43 months. Ninetytwo (63%) patients were treated with CDDP and 55 (37%) with C225. T-stage, N-stage, smoking, and alcohol consumption were well balanced between the two groups. There were more patients greater than 70 yrs of age in the C225 group (22% vs 6%, p < 0.001) and more HPVpatients (44% vs 25%, p Z 0.03). The 2-year cumulative incidence of locoregional failure (LRF) was significantly higher with C225 compared to CDDP (41.9% vs 12.6%, p < 0.001). Subgroup analysis of patients by HPV status revealed increased 2-yr LRF with C225 in HPV+ patients (33.6% vs 10.4%, p Z 0.02) and in HPVpatients (52.6% vs 20.3%, p Z 0.02). MVA of LRF adjusting for HPV, T Stage, and N Stage continued to show improved outcomes with CDDP (HR Z 0.26, p Z 0.002). The 2-year DFS was also significantly worse with C225 compared to CDDP (38.6% vs 82.6%, p < 0.001). Subgroup analysis by HPV again revealed worse 2-yr DFS with C225 in HPV+ (46.4% vs 84.8%, p < 0.001) and HPVpatients (29.2 vs 74.9%, p < 0.001). MVA of DFS adjusting for HPV, Age, T stage, N Stage, and smoking demonstrated improved DFS with CDDP (HR Z 0.31, p < 0.001). Results for OS were similar. Conclusions: Loco-regional control and DFS are significantly improved with concurrent cisplatin as compared to cetuximab in definitive RT for HNSCC. Both HPV+ and HPV patients benefit from CDDP-based concurrent therapy in LA-HNSCC. Author Disclosure: N. Riaz: None. A. Baschnagel: None. D. Adkins: E. Research Grant; Lilly. S. Rao: None. J. Huang: None. P. Chen: None. J. Ley: None. D. Krauss: None. W. Thorstad: None. N. Lee: None.

Target volume for postoperative radiotherapy in non-small cell lung cancer: Results from a prospective trial

Background and purposeA previous prospective trial reported that three-dimensional conformal postoperative radiotherapy (PORT) for pN2 NSCLC patients using a limited clinical target volume (CTV) had a late morbidity rate and pulmonary function that did not differ from those observed in pN1 patients treated with surgery without PORT. The aim of this study was to assess locoregional control and localization of failure in patients treated with PORT. Materials and methodsThe pattern of locoregional failure was evaluated retrospectively in 151 of 171 patients included in the PORT arm. The CTV included the involved lymph node stations and those with a risk of invasion >10%. Competing risk analysis was used to assess the incidence of locoregional failure and its location outside the CTV. ResultsOverall survival at 5years was 27.1% with a median follow-up of 67months for 40 living patients. The 5-year cumulative incidence of locoregional failure was 19.4% (95% CI: 18.2–20.5%) including a failure rate of 2% (95% CI: 0–17%) in locations outside or at the border of the CTV. ConclusionsThe use of limited CTV was associated with acceptable risk of geographic miss. Overall locoregional control was similar to that reported by other studies using PORT for pN2 patients.

18F-FDG PET Provides High-Impact and Powerful Prognostic Stratification in the Staging of Merkel Cell Carcinoma: A 15-Year Institutional Experience

Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with limited evidence on the role of PET scanning. The primary aim of this study was to assess the impact of (18)F-FDG PET in the staging and management of MCC. A single-institution review using clinical outcome data collected until February 2012 was performed of patients with MCC who underwent staging PET scanning between January 1997 and October 2010. Management plans were recorded prospectively at the time of the PET request, and follow-up outcomes were recorded retrospectively. The clinical impact of PET was scored using our previously published criteria: "high" if the PET scan changed the primary treatment modality or intent; "medium" if the treatment modality was unchanged but the radiation therapy technique or dose was altered. The primary objective was to test the hypothesis that the true proportion of patients who have a high- or medium-impact scan would be greater than 25%. The median follow-up of 102 consecutive patients was 4.8 y. The results of staging PET had an impact on patient management in 37% of patients (P < 0.003). High- and medium-impact scans were recorded for 22% and 15% of patients, respectively. PET staging results differed from conventional staging results in 22% of patients, with PET upstaging 17% and downstaging 5%. The 3- and 5-y overall survival was 60% (95% confidence interval, 50%-71%) and 51% (95% confidence interval, 41%-64%), respectively. In stratification by PET-defined stage, the 5-y overall survival was 67% for patients with stage I/II disease but only 31% for patients with stage III disease (log-rank P < 0.001). The 5-y cumulative incidence of locoregional failure, distant failure, and death was 16.6%, 22.3% and 14.3%, respectively. On multivariate analysis, only PET stage (P < 0.001) and primary treatment modality (P = 0.050) were significantly associated with overall survival. The primary treatment modality was not associated with progression-free survival when stratification was by tumor stage. The use of (18)F-FDG PET scans had a great impact on patients and may play an important role in the prognostic stratification and treatment of this disease.

Patterns of failure after postoperative radiotherapy for incompletely resected (R1) non-small cell lung cancer: Implications for radiation target volume design

ObjectiveOverall survival (OS) and pattern of failure in R1-resected non-small cell lung cancer (NSCLC) patients treated with 3D-planned postoperative radiotherapy (PORT) was retrospectively evaluated. The outcomes and patterns of failure in patients with (+) and without (−) extracapsular nodal extension (ECE) were compared and analyzed with respect to the radiation target volume design. Materials and methodsEighty R1-resected (37 ECE+ and 43 ECE−) patients received PORT (60Gy, 2Gy daily) between 2002 and 2011. Patients with N2 disease received limited elective nodal irradiation (ENI); for pN0-1 disease the use of ENI was optional. Among ECE− (extranodal-R1) patients there were 35 pN0-1 and eight pN2 cases; in pN0-1 patients, patterns of failure and outcomes were analyzed with respect to the use of ENI. Loco-regional failure (LRF) was defined as in-field relapse; isolated nodal failure (INF) was defined as out-of-field regional nodal recurrence occurring without LRF, irrespective of distant metastases. ResultsThe actuarial 3-year OS rate was 36.3% (median: 30 months). Three-year OS rates in the ECE− and ECE+ group were 40.4% and 31.4%, with median OS of 31 and 24 months, respectively (p=0.43). In multivariate analysis, the presence of ECE was correlated with OS (HR=3.02; 95% CI: 1.00–9.16; p=0.05). Three-year cumulative incidence of LRF (CILRF) was 14.5% and 15.5% in the ECE− and ECE+ groups, respectively (p=0.98). Three-year cumulative incidence of INF (CIINF) was 14.1% in the ECE− group and 11.1% in the ECE+ group (p=0.76). For pN0-1 patients treated with and without ENI (13 and 22 patients) 3-year CILRF rates were 7.7% and 20.8%, respectively (p=0.20); 3-year CIINF rates were 9.1% and 16.3%, respectively (p=0.65). ConclusionPORT resulted in a relatively good survival of R1-resected NSCLC patients. Relatively high incidence of INF was found in both ECE+ and ECE− patients. For ECE+ patients, treated with limited ENI, distant failure remains a major concern, so the design of ENI fields seems of lesser importance. Omission of ENI in pN0-1 (extranodal-R1) patients resulted in an unacceptably high incidence of INF. We postulate the use of some form of ENI in this setting.

Selective radiotherapy for the treatment of head and neck Merkel cell carcinoma

The role of radiotherapy (RT) in the management of Merkel cell carcinoma (MCC) is controversial. The authors of this report evaluated the rates and patterns of failure in a selected group of patients who underwent RT for MCC of the head and neck (HN). The records of 145 consecutive patients with MCC of the HN who presented to the authors' institution between 1988 and 2009 were reviewed. Only patients who received RT at the institution were included. The cumulative incidence of locoregional failure (LRF), distant metastatic failure (DMF), disease progression (DP) and disease-specific death (DSD) were estimated with death as a competing risk. Forty-eight patients were identified. The median follow-up was 51 months (range, 6-220 months) for living patients. LRF developed in 5 patients (10%), and those patients had a median time to recurrence of 3 months. Two of the 5 LRFs were local and developed at the edge of the treatment field; the remaining 3 LRFs were in lymph nodes and occurred outside the treatment field. DMF developed in 12 patients (25%). The estimated 5-year cumulative incidences of LRF, DP, and DSD were 10%, 30%, and 21%, respectively. Acute toxicities included 5 episodes (10%) of grade 3 dermatitis and 1 episode (2%) of grade 3 mucositis. The authors report a site-specific series of patients with HN MCC who received RT. In this group of patients with adverse features, RT was well tolerated, and LRF was low. The propensity for MCC to recur at the edge of the treatment field suggests that generous margins are appropriate when RT is administered.