Cancer. 2008 Aug 21;
Lacey JV, Mutter GL, Nucci MR, Ronnett BM, Ioffe OB, Rush BB, Glass AG, Richesson DA, Chatterjee N, Langholz B, Sherman ME
BACKGROUND.: Histopathologic diagnosis of endometrial biopsies is used to estimate the risk of progression to carcinoma and guide clinical management. Problems with the widely used World Health Organization (WHO) system for classifying endometrial hyperplasia (EH) have prompted the development of an alternative system based on endometrial intraepithelial neoplasia (EIN). The authors estimated progression risk associated with EIN among endometrial biopsies in a nested case-control study of EH progression. METHODS.: Index biopsies with original community pathology diagnoses of disordered proliferative endometrium (DPEM) or EH that were independently confirmed by a panel of pathologists were independently reviewed and assigned EIN classifications (inadequate, benign, EIN, or cancer) by a second panel of pathologists. Cases (N = 138) progressed to carcinoma at least 1 year (median, 6 years) after their index biopsy. Controls (N = 241) also had EH, did not progress to carcinoma, and were individually matched to cases based on age at EH, date of EH, and length of follow-up. By using conditional logistic regression, the authors estimated relative risks (RRs) with 95% confidence intervals (95% CIs) for progression to carcinoma for EIN versus benign. RESULTS.: In the EIN system, 71 (52.6%) cases and 159 (66.8%) controls were classified as benign and 42 (31.1%) cases and 65 (27.3%) controls were classified as EIN. The RR for EIN versus benign was 7.76 (95% CI, 3.36-17.91). In the WHO system, the RR for atypical hyperplasia (AH) versus DPEM, simple hyperplasia, or complex hyperplasia was 9.19 (95% CI, 3.87-21.83). CONCLUSIONS.: Among women observed for at least 1 year after receiving a biopsy-based EH diagnosis, EIN and AH were both found to have similarly increased risks of progression to carcinoma. Cancer 2008. (c) Published 2008 by American Cancer Society.
Cancer. 2008 Aug 21;
Tarhini AA, Kirkwood JM, Gooding WE, Moschos S, Agarwala SS
BACKGROUND.: Previous biochemotherapy regimens for metastatic melanoma have required attenuated dosages of interleukin 2 (IL-2) that may have compromised efficacy. METHODS.: In a phase 2 study, the authors tested sequential temozolomide (75 mg/m(2) per day orally for 3 weeks) followed by high-dose, IL-2 (600,000 U/kg per dose intravenously; maximum, 14 doses over 5 days). RESULTS.: Thirty-eight patients with treatment-naive American Joint Committee on Cancer stage IV melanoma (8 patients with M1a disease, 6 patients with M1b disease, and 24 patients with M1c disease) were enrolled. Ten patients had a history of treated brain metastases. Thirty-one patients who received at least 2 cycles of IL-2 were evaluable for response. Grade 3 toxicities included hyperbilirubinemia (9 patients), hematologic toxicities (leukopenia in 5 patients, thrombocytopenia in 3 patients), diarrhea (2 patients), and oliguria (1 patient). One patient had grade 4 nausea. The overall response rate (ORR) was 16% and included 3 complete responses that lasted 10.8 months, >/=32 months, and >/=36 months and 2 partial responses that lasted 13 months and 14 months. Responses were observed in patients with M1a disease and in patients with M1c disease. Sixteen patients had stable disease (15 patients progressed). The median progression-free survival (PFS) was 5.3 months (95% confidence interval [CI], 3.7-7.5 months). The probability of PFS at 6 months was 0.52 (95% CI, 0.33-0.67). Among 38 enrolled patients, 16 patients remained alive at a median follow-up of 6.7 months (range, 1.9-36.1 months). The median overall survival (OS) was 12.1 months (95% CI, 9.1-16.4 months), and the probability of 12-month OS was 0.54 (95% CI, 0.34-0.70 months). CONCLUSIONS.: The current results indicated that it is safe to administer HD IL-2 sequentially with temozolomide and that this combination has lower toxicity than previously used concurrent biochemotherapy regimens. However, The ORR and the durability of responses with this combination did not exceed those of single-agent HD IL-2. Cancer 2008. (c) 2008 American Cancer Society.
Head Neck. 2008 Aug 21;
Gross ND, Patel SG, Carvalho AL, Chu PY, Kowalski LP, Boyle JO, Shah JP, Kattan MW
BACKGROUND.: The application of appropriate adjuvant treatment after surgery for oral cavity squamous cell carcinoma (OCSCC) is predicated on accurate patient risk stratification. METHODS.: A nomogram for estimating locoregional recurrence-free survival (LRFS) after treatment of OCSCC was constructed from a cohort of 590 patients with OCSCC who were treated at Memorial Sloan-Kettering Cancer Center (MSKCC). The nomogram was validated using a series of 417 patients with OCSCC who were treated at Hospital do Cancer AC Camargo (HACC) in São Paulo, Brazil. RESULTS.: Despite significant differences between the MSKCC and HACC cohorts, the nomogram was able to predict LRFS from OCSCC with a concordance index of 0.693. Further statistical analysis showed that the nomogram was well calibrated. CONCLUSIONS.: This preliminary nomogram is the first prognostic model developed and externally validated to predict the likelihood of LRFS after treatment for an individual patient with OCSCC and may have practical utility for deciding adjuvant treatment. (c) 2008 Wiley Periodicals, Inc. Head Neck, 2008.
Head Neck. 2008 Aug 21;
Jäghagen EL, Bodin I, Isberg A
BACKGROUND.: Swallowing disorders following treatment for oral and pharyngeal cancer are mainly considered a surgical sequel. The recent finding that radiotherapy-induced decline in intraoral sensory abilities established an incentive to elucidate any association between the degree of sensory decline and the degree of swallowing dysfunction. METHODS.: Oral and pharyngeal swallowing was cineradiographically examined in 15 patients with oral or pharyngeal cancer before and after treatment. The patients were also tested for intraoral sensation, shape recognition, and hole size identification. RESULTS.: Swallowing function deteriorated in 67% of the patients 6 months posttreatment, with no significant improvement after 12 months. The degree of swallowing dysfunction was statistically significantly associated with the degree of diminished intraoral sensation and shape recognition. CONCLUSION.: In the quest for rehabilitation after treatment for oral and pharyngeal cancer, the impact of impaired intraoral sensation and discrimination ability on swallowing function should be taken into consideration. (c) 2008 Wiley Periodicals, Inc. Head Neck, 2008.
Head Neck. 2008 Aug 21;
Rieger JM, Zalmanowitz JG, Li SY, Tang JL, Williams D, Harris J, Seikaly H
BACKGROUND.: Measurement of functional outcomes related to different methods of soft palate reconstruction is necessary to determine efficacy of surgical intervention after resection for oropharyngeal cancer. METHODS.: Speech data were collected across 4 evaluation times for 4 groups of patients (2 groups consisted of patients with </= half the soft palate resected followed by conventional reconstruction; 2 groups consisted of patients with half or more of the soft palate resected followed by reconstruction with an adhesion or the soft palate insufficiency repair (SPIR). RESULTS.: Sixty-two patients were included. Speech was preserved when conventional reconstructive procedures were used to close smaller defects. For larger defects, reconstruction with an adhesion resulted in poorer speech outcomes than the SPIR. The SPIR group achieved normal speech results at all points of evaluation. CONCLUSIONS.: The results demonstrate that the SPIR is emerging as an efficacious surgical technique for reconstruction of larger soft palate defects. (c) 2008 Wiley Periodicals, Inc. Head Neck, 2008.
Genes Chromosomes Cancer. 2008 Aug 21;
Poonepalli A, Banerjee B, Ramnarayanan K, Palanisamy N, Putti TC, Hande MP
A study was undertaken to correlate telomere dysfunction and genomic instability with the histopathological grades and the estrogen and progesterone receptor status in breast cancer. Sixty-one archived breast tissues (38 cancer tissues and 23 paired normal tissues) were used in the study. The breast tumor tissues showed significantly shorter telomeres (7.7 kb) compared with the paired adjacent tissues (9.0 kb) by Southern blot analysis. Moreover, telomere shortening was more significant in Grade III tumors than in the Grade II tumors (P = 0.05). Quantitative fluorescence in situ hybridization on paraffin tissue sections revealed a similar trend in telomere shortening. Telomere attrition was associated with telomere dysfunction as revealed by the presence of significantly higher anaphase bridges in tumor cells which was tumor grade dependent. Furthermore, estrogen receptive negative tumors displayed higher anaphase and internuclear bridges. Selected samples from each grade showed greater genomic imbalances in the higher grades than the lower grade tumors as detected by array-comparative genomic hybridization. Telomerase activity was found to be higher in the higher grades (Grade II and III) compared with the lower grade (Grade I). The average mRNA expression of TRF1 and POT1 was lower in the tumor tissues than in the normal tissues. Tankyrase 1 mRNA expression showed a grade-dependent increase in tumor tissues and its expression was also high in estrogen and progesterone negative tumors. The data support the notion that telomere dysfunction might be of value as a marker of aggressiveness of the tumors in breast cancer patients. (c) 2008 Wiley-Liss, Inc.
