Platinum-based regimens versus cetuximab in definitive chemoradiation for human papillomavirus-unrelated head and neck cancer.

For patients ineligible for cisplatin with definitive radiotherapy (CP-CRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), concurrent cetuximab (C225-RT) is a popular substitute. Carboplatin-based chemoradiation (CB-CRT) is another option; however, relative efficacies of CP-CRT, CB-CRT and C225-RT are unclear, particularly in the human papillomavirus (HPV)-unrelated population. We identified 316 patients with stage III-IVB cancers of the oropharynx (24.7%), larynx (58.2%) and hypopharynx (17.1%) undergoing definitive C225-RT (N = 61), CB-CRT (N = 74) or CP-CRT (N = 181). Kaplan-Meier and cumulative incidence functions were generated to estimate overall survival (OS), locoregional failure (LRF) and distant metastasis (DM). Cox proportional hazards were used to determine the association of survival endpoints with clinical characteristics. Respectively, 3-year cumulative incidences for CP-CRT, CB-CRT and C225-RT were: LRF (0.19, 0.18 and 0.48, p ≤ 0.001), DM (0.17, 0.12 and 0.25, p = 0.32). Kaplan-Meier estimates for 3 year OS were: CP-CRT: 71%; CB-CRT: 59% and C225-RT: 54%; p = 0.0094. CP-CRT (hazard ratio [HR] 0.336; 95% confidence interval [CI] 0.203-0.557, p < 0.01) and CB-CRT (HR 0.279; 95% CI 0.141-0.551, p < 0.01) were associated with reduced hazard for LRF on multivariable analysis. CP-CRT (HR 0.548; 95% CI 0.355-0.845, p < 0.01) and CB-CRT (HR 0.549; 95% CI 0.334-0.904, p = 0.02) were associated with a reduced hazard for death on multivariable analysis. Propensity matching confirmed reduced hazards with a combined CP/CB-CRT group compared to C225-RT for LRF: HR 0.384 (p = 0.018) and OS: HR 0.557 (p = 0.045) and CB-CRT group compared to C225-RT for LRF: HR 0.427 (p = 0.023). In conclusion, CB-CRT is an effective alternative to CP-CRT in HPV-unrelated LA-HNSCC with superior locoregional control and OS compared to C225-RT.

A series of typical and atypical cases of Bazex syndrome: Identifying the red herring to avoid delaying cancer treatment.

Bazex syndrome is a rare paraneoplastic dermatosis that precedes diagnosis of cancer. Awareness of this syndrome is important, as it allows early detection of underlying malignancy and may prevent misdiagnosis and delays in cancer treatment.

Clinical outcomes and prognostic factors in cisplatin versus cetuximab chemoradiation for locally advanced p16 positive oropharyngeal carcinoma.

OBJECTIVES: Randomized trials evaluating cisplatin versus cetuximab chemoradiation (CRT) for p16+ oropharyngeal cancer (OPC) have yet to report preliminary data. Meanwhile, as a preemptive step toward morbidity reduction, the off-trial use of cetuximab in p16+ patients is increasing, even in those who could potentially tolerate cisplatin. The purpose of this study was to compare the efficacy of cisplatin versus cetuximab CRT in the treatment of p16+ OPC and to identify prognostic factors and predictors of tumor response. MATERIALS AND METHODS: Cases of p16+ OPC treated with cisplatin or cetuximab CRT at our institution from 2010 to 2014 were identified. Recursive partitioning analysis (RPA) classification was used to determine low-risk (LR-RPA) and intermediate-risk (IR-RPA) groups. Log-rank/Kaplan-Meier and Cox Regression methods were used to compare groups. RESULTS: We identified 205 patients who received cisplatin (n = 137) or cetuximab (n = 68) CRT in the definitive (n = 178) or postoperative (n = 27) setting. Median follow-up was 3 years. Cisplatin improved 3-year locoregional control (LRC) [92.7 vs 65.4%], distant metastasis-free survival (DMFS) [88.3 vs 71.2%], recurrence-free survival (RFS) [86.6 vs 50.6%], and overall survival (OS) [92.6 vs 72.2%] compared to cetuximab [all p < .001]. Concurrent cisplatin improved 3-year OS for LR-RPA (97.1 vs 80.3%, p < .001) and IR-RPA (97.1 vs 80.3%, p < .001) groupings. CONCLUSION: When treating p16+ OPC with CRT, the threshold for substitution of cisplatin with cetuximab should be maintained appropriately high in order to prolong survival times and optimize locoregional and distant tumor control. When cetuximab is used in cisplatin-ineligible patients, altered fractionation RT should be considered in an effort to improve LRC.

Sinonasal adenoid cystic carcinoma: Treatment outcomes and association with human papillomavirus.

BACKGROUND: The purpose of this study was to review long-term outcomes of sinonasal adenoid cystic carcinoma (ACC) and to clarify its association with human papillomavirus (HPV). METHODS: The medical records of 23 patients with sinonasal ACC treated with primary surgical resection between 1998 and 2013 were reviewed. Tissue specimens were available for 17 patients. The p16 testing was performed using immunohistochemistry (IHC), and HPV infection was determined using quantitative polymerase chain reaction (PCR) with primers targeting the E6/E7 region. RESULTS: Two of the 17 samples showed strong and diffuse p16 staining, whereas the remaining 15 cases showed p16-positivity isolated to the luminal cells. Only one of the p16-positive cases was positive for HPV. The 5-year local failure, disease-free survival (DFS), and overall survival (OS) were 51%, 52%, and 62%, respectively. CONCLUSION: Local failures are common with advanced sinonasal ACC, and the association of HPV with true sinonasal ACC is low.

The role of radiation therapy in uterine-confined endometrial carcinoma.

The treatment of endometrial cancer begins with surgery, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal lavage, and a consideration for lymph node evaluation. Selection of adjuvant therapy is based on an approximation of the risk of recurrence with features such as stage, tumor histology, lymphovascular space invasion, and patient age. The role of adjuvant radiation therapy in patients with intermediate risk of recurrence is a matter of ongoing controversy. Several randomized trials indicate that adjuvant radiation therapy improves loco-regional control. However, the ideal form of radiation therapy in these patients continues to be under debate.

Residents' educational needs during transition into radiation oncology residency.

PURPOSE: The aim of this study was to assess current practices, strengths, and deficiencies in the orientation process for incoming radiation oncology (RO) residents. METHODS: An institutional review board-approved anonymous survey was distributed electronically to RO residents in postgraduate years 2 to 5 and those in their first postgraduate years. Questions were included on the type and utility of orientation materials received by residents before and upon entering RO residency. RESULTS: Responses were received from 25.3% of all current and recent residents. Most residents (81.3%) had 2 or 3 months of prior experience rotating in clinical RO. Orientation materials in RO were received by 74.1% of residents before starting residency. An orientation at the start of RO residency was received by 95.4% of RO residents. Orientation length was <1 hour in 2.8%, 1 hour to a half day in 7.8%, more than a half day but <1 full day in 21.8%, >1 full day but <1 week in 45.8%, and >1 week but <1 month in 20.1%. Almost half of RO residents (48.4%) felt that an RO orientation was essential, but only 11.3% of residents felt that their orientation programs were essential. A statistically significant Spearman's correlation was observed between programs with longer orientation and increased helpfulness of orientation (ρ = 0.26, P = .008). Residents with more components in their onsite orientations felt that their orientations were more helpful (ρ = 0.407, P < .001). CONCLUSIONS: Radiation oncology residents could benefit from a more comprehensive orientation, including a broader array of materials sent to incoming residents for their review before starting residency and a more extensive onsite orientation.

Change in creatinine clearance over time following upper abdominal irradiation: a dose-volume histogram multivariate analysis.

OBJECTIVES: To investigate the change in creatinine clearance (CrCl) over time following upper abdominal radiation utilizing a dose-volume histogram (DVH) multivariate analysis. METHODS: The study population included 125 patients with gastrointestinal malignancy treated with abdominal radiation therapy at our institution between 1994 and 2006, with available creatinine and DVH information. Kidney dose-volume data collected included mean kidney dose, volume of kidney irradiated, V5, V10, and V20 of total kidney volume, and number of mL of kidney greater than and less than 20 Gy. RESULTS: With a median follow-up of 2.4 years, and a mean kidney dose of 16.2 Gy, a significant correlation between decrease in CrCl and irradiated kidney volume observed was noted for all DVH parameters. The strongest correlations were found when using V5, V10, and number of mL of kidney treated to greater than 20 Gy. There was no significant change in number of antihypertensive medications taken by patients over time, and no relationship between outcome variables and pre-existing comorbidities. CONCLUSIONS: This is the first study that we are aware of comparing DVH data with measurement of renal toxicity. We show significant correlations between dose and volume irradiated and decline in renal function. This will be clinically useful when determining a treatment plan for patients with borderline preradiation CrCl and provides evidence that minimizing radiation to the kidney could have important clinical ramifications.

The kinetics of translocation of Smac/DIABLO from the mitochondria to the cytosol in HeLa cells.

Smac (second mitochondrial activator of caspases) is released from the mitochondria during apoptosis to relieve inhibition of caspases by the inhibitor of apoptosis proteins (IAPs). The release of Smac antagonizes several IAPs and assists the initiator caspase-9 and effector caspases (caspase-3, caspase-6, and caspase-7) in becoming active, ultimately leading to death of the cell. Translocation of Smac along with cytochrome c and other mitochondrial pro-apoptotic proteins represent important regulatory checkpoints for mitochondria-mediated apoptosis. Whether Smac and cytochrome c translocate by the same mechanism is not known. Here, we show that the time required for Smac efflux from the mitochondria of cells subjected to staurosporine-induced apoptosis is approximately four times longer than the time required for cytochrome c efflux. These results suggest that Smac and cytochrome c may exit the mitochondria by different pathways.