[Show abstract][Hide abstract]ABSTRACT: Purpose:
Epidemiologic studies have identified an increasing incidence of squamous cell carcinoma of the oral tongue (SCCOT) in younger patients.
DNA isolated from tongue tumors of young (<45 years, non-smokers) and old (>45 years) patients at was subjected to whole-exome sequencing and copy-number analysis. These data were compared with data from similar patients in the TCGA (The Cancer Genome Atlas) project.
In this study, we found that gene-specific mutation and copy-number alteration frequencies were similar between young and old patients with SCCOT in two independent cohorts. Likewise, the types of base changes observed in the young cohort were similar to those in the old cohort even though they differed in smoking history. TCGA data also demonstrate that the genomic effects of smoking are tumor site-specific, and we find that smoking has only a minor impact on the types of mutations observed in SCCOT.
Overall, tumors from young patients with SCCOT appear genomically similar to those of older patients with SCCOT, and the cause for the increasing incidence of young SCCOT remains unknown. These data indicate that the functional impact of smoking on carcinogenesis in SCCOT is still poorly understood.
Full-text available · Article · May 2014 · Clinical Cancer Research
[Show abstract][Hide abstract]ABSTRACT: The role of radiotherapy after surgery for myxopapillary ependymoma (MPE) is unclear.
To review long-term outcomes after surgery, with or without radiation, for spinal MPE.
51 patients with spinal MPE treated from 1968[FIGURE DASH]2007 were included. Associations between clinical variables and overall survival (OS), progression-free survival (PFS), and local control (LC) were tested with Cox regression analysis.
Median age at diagnosis was 35 years (range 8[FIGURE DASH]63). Twenty patients (39%) had surgery alone, 30 (59%) had surgery plus radiation, and 1 (2%) had radiation only. At a median follow-up of 11 years (range 0.2[FIGURE DASH]37), 10-year OS, PFS, and LC for the entire group were 93%, 63%, and 67%. Nineteen patients (37%) had disease recurrence, and the recurrence was mostly local (79%). Twenty-eight of 50 patients who had surgery (56%) had gross total resection; 10-year LC was 56% after surgery versus 92% after surgery and radiation (log-rank P=0.14); median time of LC was 10.5 years for patients receiving gross total resection plus RT, and 4.75 years for gross total resection only (P=0.03). Among 16 patients with subtotal resection and follow-up data, 10-year LC was 0% after surgery vs. 65% for surgery plus radiation (log rank P=0.008). In multivariate analyses adjusting for resection type, age >35 at diagnosis and receipt of adjuvant radiation were associated with improved PFS (hazard ratio (HR)=0.14, P=0.003 and HR=0.45, P=0.009) and LC (HR=0.22, P=0.02 and HR=0.45, P=0.009).
Postoperative radiotherapy after resection of MPE was associated with improved PFS and LC.
[Show abstract][Hide abstract]ABSTRACT: Objectives:
We previously reported survival trends among patients with inflammatory breast cancer (IBC) over a 30-year period before 2005. Here we evaluated survival outcomes for women with IBC diagnosed before or after October 2006, in the era of HER2-directed therapy and after opening a dedicated multidisciplinary IBC clinic.
We retrospectively identified and reviewed 260 patients with newly diagnosed IBC without distant metastasis, 168 treated before October 2006 and 92 treated afterward. Most patients received anthracycline and taxane-based neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Survival outcomes were compared between the 2 groups.
Median follow-up time was 29 months for the entire cohort (39 and 24 mo for patients treated before and after October 2006). Patients treated more recently were more likely to have received neoadjuvant HER2-directed therapy for HER2-positive tumors (100% vs. 54%, P=0.001). No differences were found in receipt of hormone therapy. Three-year overall survival rates were 63% for those treated before and 82% for those treated after October 2006 (log-rank P=0.02). Univariate Cox analysis demonstrated better overall survival among patients treated after October 2006 than among those treated beforehand (hazard ratio [HR] 0.5; 95% confidence interval [CI], 0.34-0.94); a trend toward improved survival was noted in the multivariate analysis (HR=0.47; 95% CI, 0.19-1.16; P=0.10). Significant factors in the multivariate model included HER2-directed therapy (HR=0.38; 95% CI, 0.17-0.84; P=0.02) and estrogen receptor positivity (HR=0.32; 95% CI, 0.14-0.74; P=0.01).
Survival improved in the context of the IBC clinic and prompt initiation of neoadjuvant HER2-directed therapeutics.
Article · May 2013 · American journal of clinical oncology
[Show abstract][Hide abstract]ABSTRACT: Objective:
We previously found that galectin-7 was upregulated in patients with cervical cancer who remained recurrence-free after chemoradiation. We hypothesized that pretreatment levels of galectin-7 predict radiation response in patients with squamous cell carcinoma (SCC) of the cervix.
Galectin-7 expression was assessed by immunohistochemical staining of a tissue microarray of paraffin-embedded specimens from 161 patients with cervical SCC treated with definitive radiation therapy in 1980-1999. Galectin-7 expression was scored as absent or present. Distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were computed using the Kaplan-Meier method and log-rank tests.
The median age at diagnosis was 45 years (range 21-85) and median follow-up interval was 71 months (range 0-285). Of the 161 patients, 105 (65%) had FIGO stage IB disease, 18 (11%) stage IIA, and 38 (24%) stage IIB. Median tumor diameter was 5.5 cm (range 3.5-8). Seven patients (4%) received concurrent chemotherapy; 139 patients (86%) had galectin-7-positive tumors and 22 (14%) galectin-7-negative tumors. Five-year DMFS rates for patients with galectin-7-positive versus -negative tumors were 73% and 55% (p=0.05); DSS, 65% and 36% (p=0.004); and OS, 64% and 36% (p=0.005). In multivariate analysis adjusting for age, stage, and tumor diameter, galectin-7 expression remained a significant predictor of DMFS (hazard ratio [HR]=0.43, p=0.03), DSS (HR=0.34, p=0.001), and OS (HR=0.34, p=0.001).
Elevated galectin-7 expression is associated with improved outcomes after radiation therapy for cervical cancer. Further studies are required to validate these findings and clarify the role of galectin-7 in disease progression and radiation response.
[Show abstract][Hide abstract]ABSTRACT: Purpose:
To determine the association between radiation doses delivered to the mandible and the occurrence of osteoradionecrosis (ORN).
Methods and materials:
We reviewed the records of 402 oropharyngeal cancer patients with stage T1 or T2 disease treated with definitive radiation between January 2000 and October 2008 for the occurrence of ORN. Demographic and treatment variables were compared between patients with ORN and those without. To examine the dosimetric relationship further, a nested case-control comparison was performed. One to 2 ORN-free patients were selected to match each ORN patient by age, sex, radiation type, treatment year, and cancer subsite. Detailed radiation treatment plans for the ORN cases and matched controls were reviewed. Mann-Whitney test and conditional logistic regression were used to compare relative volumes of the mandible exposed to doses ranging from 10 Gy-60 Gy in 10-Gy increments.
In 30 patients (7.5%), ORN developed during a median follow-up time of 31 months, including 6 patients with grade 4 ORN that required major surgery. The median time to develop ORN was 8 months (range, 0-71 months). Detailed radiation treatment plans were available for 25 of the 30 ORN patients and 40 matched ORN-free patients. In the matched case-control analysis, there was a statistically significant difference between the volumes of mandible in the 2 groups receiving doses between 50 Gy (V50) and 60 Gy (V60). The most notable difference was seen at V50, with a P value of .02 in the multivariate model after adjustment for the matching variables and dental status (dentate or with extraction).
V50 and V60 saw the most significant differences between the ORN group and the comparison group. Minimizing the percent mandibular volume exposed to 50 Gy may reduce ORN risk.
Article · Jul 2012 · International journal of radiation oncology, biology, physics