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We studied the immunohistochemical expression of HER-2/neu, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), estrogen receptor (ER), and progesterone receptor (PR) in uterine cervical small cell and large cell neuroendocrine carcinomas (SCNECs and LCNECs) from 24 patients seen at The University of Texas M.D. Anderson Cancer Center. The objectives were to determine their expression and prognostic role in survival. Twenty-three cases (95.8%) expressed VEGF. The tumors expressing EGFR, HER-2/neu, and COX-2 were modest in numbers: eight (33.3%), 10 (41.7%), and seven (29.2%), respectively. Only one tumor (4.2%) expressed ER, and only two tumors (8.3%) expressed PR. No significant differences in the expression of these factors were found between SCNECs and LCNECs or between stage I and stage II–III tumors. The median overall survival was 21.1 months (95% confidence interval [CI], 17.2–25.0 months). Only HER-2/neu expression was significantly associated with survival. Patients with negative HER-2/neu expression tumors had significantly shorter survival than those whose tumors were positive, 14.2 months (95% CI, 10.6−17.7 months) versus 33.1 months (95% CI, 0−76.92 months) (P = 0.03). There was a trend toward worse survival in patients with EGFR expression, but this finding was not significant. The combination of negative HER-2/neu expression and positive EGFR expression had the worst impact on survival.

We investigated the time course of central disease recurrence (CDR) in 2997 patients treated with radiation for stage I–II squamous cell carcinoma of the cervix. CDR rates were 6.8%, 7.8%, and 9.6%, at 5, 10, and 20 years, respectively. The risk of CDR was independently correlated with tumor size (P < 0.0001) but not with FIGO stage. The hazard rate peaked in the first year of follow-up and then fell steeply; after 3 years, the hazard rate was approximately constant at 0.2–0.4% per year. Although after 3 years the risk of CDR was low, it continued to be slightly greater for patients with tumors ≥5 cm than for those with smaller tumors (P = 0.001). Patients who had CDR <36 months after treatment were less likely to be candidates for salvage therapy and had a poorer postrecurrence survival rate than those with recurrence ≥36 months after treatment (4.5% versus 42.1%, P < 0.0001). The higher rate of CDR in the first 3 years and the poor survival after early recurrence suggest that most early CDRs are true relapses. The relatively stable annual actuarial risk between 3 and 25 years and the better survival rate after late CDR suggest that most “recurrences” after 3 years are actually new neoplasms.

The purpose of this study was to evaluate overall survival (OS) and determine prognostic subclassifications for stage IIIA endometrial cancer. Stage IIIA endometrial cancer patients treated at M.D. Anderson Cancer Center from 1989 to 2002 were reviewed. Clinical information was obtained from the medical record. Cox regression analyses were performed to evaluate the association of pathologic criteria and OS. Patients were divided into four groups based on this analysis: E1, endometrioid/pelvic cytology only; E2, endometrioid/adnexa ± serosal spread; NE1, nonendometrioid/pelvic cytology only; and NE2, nonendometrioid/adenexa ± serosal spread. Forty-nine patients were identified. By multivariate analysis, histology and extent of disease were the only factors associated with OS. Five-year OS in the four subgroups based on histology and extent of disease were: E1, 79%, E2, 65%, NE1, 64%, and NE2, 13%. Histologic subtype and extent of pelvic disease are the only prognostic factors associated with OS. Patients with endometrioid tumors and extent of pelvic disease limited to positive cytology had a favorable outcome, with or without adjuvant therapy. Future prospective clinical trials should consider subclassifying patients with stage IIIA disease to better evaluate the role of adjuvant therapy.

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Radiation therapy has been a major therapeutic modality for eradicating malignant tumors over the past century. In fact, it was not long after the discovery of radium that the first woman with cervical cancer underwent intracavitary brachytherapy. Progress in the way that this cytotoxic agent is manipulated and delivered has seen an explosive growth over the past two decades with technological developments in physics, computing capabilities, and imaging. Although radiation oncologists are educated in and familiar with the wealth of new revolutionary techniques, it is not easy for other key members of the team to keep up with the rapid progress and its significance. However, to fully exploit these enormous gains and to communicate effectively, medical and gynecological oncologists are expected to be aware of state-of-the-art radiation oncology. Here, we elucidate and illustrate contemporary techniques in radiation oncology, with particular attention paid to the external beam radiotherapy used for adjuvant and primary definitive management of malignancies of the female pelvis.

TXPurpose/Objective(s): As high as 30-40% of patients with cervical squamous cell carcinoma (SCCC) treated with definitive cisplatin and radiation therapy (CRT) may recur after completion of treatment. Radiation response may depend on generation of an effective anti-tumor immune response and the intestinal microbiome has been shown to be essential to develop an antigen specific immune response following immunotherapy in mouse models. We examined the association of changes in cervical and rectal microbiome throughout CRT with treatment response. Materials/Methods: Patients with newly diagnosed SCCC were enrolled on a prospective study to characterize changes in the intestinal microbiome during CRT. Rectal and cervical samples were obtained from 20 patients before and during (weeks 1, 3, and 5) radiation. Microbiome was characterized via 16S rDNA sequencing. Disease response was categorized as complete response (NED) or recurrent/progressive disease (REC) on 3month follow-up PET/CT. Shannon diversity index (SDI) was used to compare microbiome diversity. Linear regression was used to evaluate changes in SDI throughout treatment. Paired samples across all four time points were analyzed with Wilcoxon signed-rank test. ROC curves were generated for SDI as a predictor of disease response. Relative abundance of specific OTUs was compared across samples using Mann Whitney U test with FDR-adjusted P-values. Results: Rectal SDI decreased throughout the course of treatment (B Z -0.07; P Z 0.038) while cervix SDI remained stable (B Z -0.007; P Z 0.88). Rectal SDI was higher for NED patients than REC patients at week 1 (NED mean 3.12 [SD Z 0.35] vs REC Mean 2.32 [SD 0.52]; P Z 0.009) and at week 3 (NED Mean 2.99 [SD 0.33] vs REC mean 2.47 [SD 0.25]; P Z 0.004) post CRT. ROC curve of SDI as a predictor of disease status yielded an AUC of 97.5%. An SDI cutoff of 2.7 at one week of treatment yielded 100% sensitivity and 75% specificity for recurrent/persistent disease at first followup. Three OTU's mapping to (genus/genera) were significantly more abundant in cervical samples from REC patients over NED patients (P < 0.0001), including two Tenericutes and one Firmicute. Five OTU's mapping were significantly more abundant in rectal samples from NED patients, including three Bacteroides (P Z 0.03 to 0.005) and two Firmicutes (P Z 0.05). Conclusion: Rectal diversity and abundance at one week of treatment exhibits 100% sensitivity and 75% specificity for predicting SCCC response to CRT. Specific intestinal genera may provide a protective effect on tumor response, while specific vaginal genera may have a deleterious effect on tumor outcome.Purpose/Objective(s): Quantification of circulating tumor cells (CTCs) has been shown to provide prognostic information in select patients with advanced cancers. Additionally, there is increasing interest in pursuing potentially curative localized therapies in patients with oligometastatic solid tumor malignancies, although there are currently no biomarkers to predict the outcome of this approach for...