To estimate the overall survival (OS) impact from increasing time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC).
Using the National Cancer Data Base ...(NCDB), we examined patients who received curative therapy for the following sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was the number of days from diagnosis to initiation of curative treatment. The effect of TTI on OS was determined by using Cox regression models (MVA). Recursive partitioning analysis (RPA) identified TTI thresholds via conditional inference trees to estimate the greatest differences in OS on the basis of randomly selected training and validation sets, and repeated this 1,000 times to ensure robustness of TTI thresholds.
A total of 51,655 patients were included. On MVA, TTI of 61 to 90 days versus less than 30 days (hazard ratio HR, 1.13; 95% CI, 1.08 to 1.19) independently increased mortality risk. TTI of 67 days appeared as the optimal threshold on the training RPA, statistical significance was confirmed in the validation set (P < .001), and the 67-day TTI was the optimal threshold in 54% of repeated simulations. Overall, 96% of simulations validated two optimal TTI thresholds, with ranges of 46 to 52 days and 62 to 67 days. The median OS for TTI of 46 to 52 days or fewer versus 53 to 67 days versus greater than 67 days was 71.9 months (95% CI, 70.3 to 73.5 months) versus 61 months (95% CI, 57 to 66.1 months) versus 46.6 months (95% CI, 42.8 to 50.7 months), respectively (P < .001). In the most recent year with available data (2011), 25% of patients had TTI of greater than 46 days.
TTI independently affects survival. One in four patients experienced treatment delay. TTI of greater than 46 to 52 days introduced an increased risk of death that was most consistently detrimental beyond 60 days. Prolonged TTI is currently affecting survival.
To assess the long-term quality of life (QoL) outcomes from a phase 3 trial comparing 2 modes of intensity modulated radiation therapy (IMRT): conventional IMRT (CIMRT) versus hypofractionated IMRT ...(HIMRT) in patients with localized prostate cancer.
Between 2002 and 2006, 303 men with low-risk to high-risk prostate cancer were randomized to 76 Gy in 38 fractions (CIMRT) versus 70.2 Gy in 26 fractions (HIMRT). QoL was compared by use of the Expanded Prostate Cancer Index Composite (EPIC), the International Prostate Symptom Score (IPSS), and EuroQoL (EQ5D) questionnaires. The primary outcome of the QoL analysis was a minimum clinically important difference defined as a 0.5 standard deviation change from baseline for each respective QoL parameter. Treatment effects were evaluated with the use of logistic mixed effects regression models.
A total of 286, 299, and 218 patients had baseline EPIC, IPSS, or EQ5D data available and were included in the analysis. Overall, there was no statistically significant difference between the 2 treatment arms in terms of EPIC, IPSS, or EQ5D scores over time, although there was a trend toward lower EPIC urinary incontinence scores in the HIMRT arm. More patients in the HIMRT arm had a lower EPIC urinary incontinence score relative to baseline versus patients in the CIMRT arm with long-term follow-up. On multivariable analysis, there was no association between radiation fractionation scheme and any QoL parameter. When other clinical factors were examined, lymph node radiation was associated with worse EPIC hormonal scores versus patients receiving no lymph node radiation. In general, QoL outcomes were generally stable over time, with the exception of EPIC hormonal and EQ5D scores.
In this randomized prospective study, there were stable QoL changes in patients receiving HIMRT or CIMRT. Our results add to the growing body of literature suggesting that HIMRT may be an acceptable treatment modality in clinically localized prostate cancer.
Skin adnexal carcinoma (SAC) is a rare cutaneous malignancy that arises from sebaceous and sweat glands. These carcinomas are believed to behave more aggressively than cutaneous squamous cell ...carcinomas (SCC) with a propensity for local recurrence. The role of adjuvant radiotherapy in SAC is undefined.
We retrospectively reviewed all cases of head and neck SAC treated with surgery and adjuvant radiation from 2000 to 2012 at a single institution.
Nine cases were identified. Median age was 67 (range, 52 to 88) years. The histologies were: adnexal carcinoma (n=1), adnexal carcinoma with sebaceous differentiation (n=1), adnexal carcinoma with squamous differentiation (n=1), skin appendage carcinoma (n=1), sclerosing sweat duct carcinoma (n=1), mucinous carcinoma (n=1), ductal eccrine adenocarcinoma (n=1), porocarcinoma (n=1), and trichilemmal carcinoma (n=1). All tumors were reviewed by a dermatopathologist to confirm the SAC diagnosis.All patients had undergone surgery. Indications for adjuvant radiation included involved lymph nodes (n=4), perineural invasion (n=2), nodal extracapsular extension (n=2), positive margin (n=1), high-grade histology (n=6), multifocal disease (n=2), and/or recurrent disease (n=5). Radiation was delivered to the primary site alone (n=3), to the draining lymphatics alone (n=2), or to both (n=4). One patient received concurrent cisplatin. Median dose to the primary site was 60 Gy and to the neck was 50 Gy.Median follow-up was 4.0 years (range, 0.6 to 11.4 y). Locoregional control was 100%. Five-year progression-free survival was 89%. There was 1 acute grade 3 toxicity and no greater than or equal to grade 2 late toxicities were recorded.
Surgery and adjuvant radiation for high-risk SAC offers excellent locoregional control with acceptable toxicity.
Highlights • Serial imaging permits estimates of tumor-specific growth rate (TSGR) for OPC. • Faster TSGR correlates well with p16 status, T-stage and smoking. • TSGR predicts outcomes for ...oropharyngeal cancer (OPC) in the HPV era. • TSGR calculation may improve identification of de-escalation candidates.
Intensity-modulated radiation therapy (IMRT) has been shown to decrease abdominal toxicity in patients undergoing chemoradiation (CRT) for pancreatic cancer. We evaluated whether IMRT impacts the ...rates of hematologic toxicity and chemotherapy dose intensity in patients undergoing CRT.
We retrospectively reviewed patients with borderline resectable or locally advanced pancreatic cancer undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of non-gemcitabine therapy, chemotherapy before CRT, or abnormal baseline hematologic indices. Endpoints included total gemcitabine dose received, dose intensity, unplanned dose reductions, and hematologic toxicity (WBC, ANC, platelet, and hemoglobin). Patient/treatment factors were evaluated for their relationship to the above endpoints during CRT and within the first 3 months post-CRT. Statistical analysis was performed using the Fisher exact test and regression models. Because of the multiple comparisons in the presented analysis, a false discovery rate adjustment was performed at the 5% false discovery rate level.
Eighty-five patients met the inclusion criteria. Fifty-eight (68.2%) patients received treatment with IMRT, and 27 (31.8%) patients were treated with 3D-conformal radiation. During CRT, there was no relationship between radiation technique and gemcitabine dose received, dose intensity, or hematologic grade 3+ toxicity. Post-CRT, there was no relationship between radiation technique and total gemcitabine dose received, dose intensity, or dose reduction. Patients receiving IMRT were more likely to have ANC grade 3+ toxicity (P=0.007) post-CRT, although this was no longer statistically significant after correction. There were no other relationships between treatment technique and hematologic toxicity.
IMRT technique may be associated with higher hematologic toxicity in patients undergoing CRT for pancreatic cancer. Given the expanding use of CRT, additional study is needed to identify the impact of IMRT on myelosuppression in these patients.
Short hairpin RNAs (shRNAs) have emerged as a novel therapeutic modality, but there is increasing concern over nonspecific effects in vivo. Here, we used viral vectors to express shRNAs against ...endogenous p53 in livers of conditional MYC-transgenic mice. As expected, the shRNAs silenced hepatic p53 and accelerated liver tumorigenesis when MYC was concurrently expressed. Surprisingly, various irrelevant control shRNAs similarly induced a rapid onset of tumorigenesis, comparable to carbon tetrachloride (CCl4), a potent carcinogen. We found that even marginal shRNA doses can already trigger histologically detectable hepatoxicity and increased hepatocyte apoptosis. Moreover, we noted that shRNA expression globally dysregulated hepatic microRNA (miRNA) expression, and that shRNA levels and activity further increased in the presence of MYC. In MYC-expressing transgenic mice, the marginal shRNA-induced liver injury sufficed to further stimulate hepatocellular division that was in turn associated with markedly increased expression of the mitotic cyclin B1. Hence, even at low doses, shRNAs can cause low-level hepatoxicity that can facilitate the ability of the MYC oncogene to induce liver tumorigenesis. Our data warrant caution regarding the possible carcinogenic potential of shRNAs when used as clinical agent, particularly in circumstances where tissues are genetically predisposed to cellular transformation and proliferation.
Micro-Abstract Data are limited regarding the efficacy of adjuvant radiation therapy (RT) alone for elderly women with low-risk breast cancer. The present study of > 500 women identified a group of ...women for whom adjuvant RT, without endocrine therapy (ET), could result in acceptable outcomes. The study also explored the influence of ET nonadherence and tumor size on outcomes.
Patients with pancreatic adenocarcinoma (PAC) are often treated with neoadjuvant chemoradiation (NACRT) in hopes of downstaging their disease for potential surgical resection. We hypothesized that ...increasing the radiation dose to the area of the tumor abutting the vessel(s) of concern would increase the rate of surgical resection in patients with borderline resectable PAC (BRPAC) and locally advanced PAC (LAPAC) treated with NACRT.
We retrospectively reviewed consecutive cases of BRPAC and LAPAC treated with NACRT from January 2006 to December 2013, with or without a vessel boost (VB), at a single institution. The primary endpoints were rate of R0/R1 potentially curative surgical resection and acute toxicity. Univariate analysis with the Fisher exact test was performed to evaluate the effect of each variable. Multiple logistic regression was used to adjust for the following covariates: year of diagnosis, age, sex, carbohydrate antigen 19-9 (CA19-9) level at diagnosis, and BRPAC or LAPAC.
Of the 104 patients identified, 22% (n = 23) received a VB (median, 54 Gy; range, 54-64 Gy), and 78% (n = 81) received no boost (median, 50.4 Gy; range, 48.6-52.2 Gy). More patients in the VB group were treated from 2010 to 2013 (P < .001) and with intensity modulated radiation therapy (P = .002). Other baseline characteristics were balanced. After adjustment for covariates, there was a statistical trend toward increased surgical resection in patients who received a VB (odds ratio OR, 2.77; 95% confidence interval CI, 0.89-8.57; P = .077). Age (≥70 years; OR, 0.42; 95% CI, 0.16-1.05; P = .064) and LAPAC (OR, 0.32; 95% CI, 0.09-1.09; P = .068) also trended toward significance. CA19-9 ≥47.9 U/mL (OR, 0.24; 95% CI, 0.08-0.71; P = .010) was significant on multivariate analysis. There was no significant difference in acute or late toxicity between groups.
In our retrospective series, dose escalation was associated with an improved surgical resection rate in BRPAC and LAPAC patients treated with NACRT, although this improvement was not statistically significant.
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