Stereotactic body radiation therapy in the treatment of ovarian cancer.

BACKGROUND: This study evaluates the outcomes and toxicity of stereotactic body radiation therapy (SBRT) in ovarian cancer. METHODS: This retrospective analysis considered all patients treated with SBRT from 2009 to 2018 with a primary ovarian tumor. Follow-up included PET-CT and CT scans at 2-3 month intervals. Statistical analysis primarily consisted of univariate analysis, Cox proportional hazards analysis, and the Kaplan-Meier method. RESULTS: The study included 35 patients with 98 treatments for lymph nodes (51), local recurrence (21), and de novo solid metastases (26). Median biologically effective dose (BED), gross tumor volume, and planning target volume were 38.40 Gy, 10.41 cc, and 25.21 cc, respectively. 52 lesions showed complete radiographic response, and two-year local control was 80%. Median overall survival (OS) was 35.2 months, and two-year progression-free survival (PFS) was 12%. On univariate analysis, Eastern Cooperative Oncology Group performance status > 0 was predictive of decreased OS (p = 0.0024) and PFS (p = 0.044). Factors predictive of local failure included lower BED (p = 0.016), treatment for recurrence (p = 0.029), and higher pre-treatment SUV (p = 0.026). Kaplan-Meier analysis showed BED ≤35 Gy (p < 0.005) and treatment for recurrence (p = 0.01) to be predictive of local failure. On Cox proportional hazards analysis, treatment of lymph nodes was predictive of complete radiographic response (hazard ratio (HR) = 4.95), as was higher BED (HR = 1.03). Toxicity included 27 cases of grade < 3 toxicity, and one grade 5 late toxicity of GI bleed from a radiation therapy-induced duodenal ulcer. CONCLUSIONS: SBRT provides durable local control with minimal toxicity in ovarian cancer, especially with BED > 35 Gy and treatment for lymph nodes.

Cervical cancer and human papillomavirus in indigenous Guyanese women.

OBJECTIVE: The purpose of this study was to determine the prevalence of cervical disease, human papillomavirus infection, and human papillomavirus (HPV) genotypes in indigenous villages of Guyana. STUDY DESIGN: This is a retrospective analysis of a clinical cervical cancer screening and treatment program: 2250 women underwent cytologic screening; 1423 women were concomitantly screened for HPV. HPV genotyping was performed in 45 women with high-grade dysplasia and in 9 women with cervical carcinoma. RESULTS: We found invasive cervical carcinoma in 0.80% of the women, cervical intraepithelial neoplasia II and III in 5.07% of the women, and a high-risk HPV infection rate in 19.3% of the women, all of which peaked between the ages of 20-30 years. Sixteen genotypes were detected in women with high-grade dysplasia or cancer: HPV 31, 25.0%; HPV 16, 22.7%; HPV 18, 13.6%. The rate of HPV 16 and 18 in cervical cancer was 55.50%. CONCLUSION: Indigenous Guyanese women have a high rate of cervical cancer and high-grade dysplasia, with an apparent predominance of HPV 16 and 18 in invasive cancer and overrepresentation of HPV 31 in high-grade dysplasia.

A multipeptide vaccine is safe and elicits T-cell responses in participants with advanced stage ovarian cancer.

Nine participants with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who were human leukocyte antigen (HLA)-A1, HLA-A2, or HLA-A3, were eligible to enroll in a phase 1 study designed to assess the safety and immunogenicity of a peptide-based vaccine. Participants received 5 class I major histocompatibility complex-restricted synthetic peptides derived from multiple ovarian cancer-associated proteins plus a class II major histocompatibility complex-restricted synthetic helper peptide derived from tetanus toxoid protein. The vaccines were administered with granulocyte macrophage-colony stimulating factor in Montanide ISA-51 adjuvant over a 7-week period. All vaccine-related toxicities were grade 1 to 2, the most common being injection site reaction (grade 2, 100%), fatigue (grade 1, 78%), and headache (grade 1, 67%). Lymphocytes from the peripheral blood and a node draining a secondary vaccine site (sentinel immunized node) were harvested during the course of vaccination and T-cell responses to the peptides were evaluated using an enzyme-linked immunosorbent spot assay. CD8 T-cell responses were detected in 1 participant ex vivo and in 8 of 9 participants (89%) after in vitro stimulation. All 4 HLA-A2 and HLA-A3-restricted peptides were immunogenic. This includes 2 peptides, folate binding protein (FBP191-199) and Her-2/neu754-762, which had not previously been evaluated in vaccines in humans. Responding T cells required over 200 nM for half-maximal reactivity. These data support continued investigation of these peptides as immunogens for patients with ovarian cancer but, owing to low potency, also suggest a need for additional immunomodulation in combination with vaccines to increase the magnitude and to improve the quality of the T-cell responses.

Cervical adenocarcinoma in situ: the predictive value of conization margin status.

OBJECTIVE: We evaluated the impact of conization margin status on outcomes of patients diagnosed with cervical adenocarcinoma in situ. STUDY DESIGN: A retrospective chart review identified patients at a University hospital from 1988-2006 with adenocarcinoma in situ (AIS) on conization. RESULTS: Seventy-four patients were included. Median follow-up was 26 months. Twenty-two of 74 patients (30%) had positive margins, 46 patients (62%) had negative margins, and 6 patients had indeterminate margins. Of patients with positive margins, 55% (12/22) were diagnosed with residual or recurrent disease, including 3 patients diagnosed with adenocarcinoma on hysterectomy. Thirteen percent of patients with negative conization margins (6/46) were diagnosed with residual or recurrent disease, including 2 patients diagnosed with adenocarcinoma during follow-up. Cold knife conization resulted in a significantly higher number of negative margins compared to other conization procedures (P = .013). CONCLUSIONS: Even with negative conization margins, women still face a risk of residual, recurrent, or invasive disease.

Predictors of suboptimal surgical cytoreduction in women treated with initial cytoreductive surgery for advanced stage epithelial ovarian cancer.

OBJECTIVE: The purpose of this study was to determine if a suboptimal cytoreduction can be predicted preoperatively in women with advanced ovarian cancer. STUDY DESIGN: All women with stage III/IV epithelial ovarian cancer treated with initial surgery at our hospital between January 1, 1995 and January 1, 2003 were eligible; 56 patients met inclusion criteria and underwent retrospective chart review. Statistical analysis was performed using SPSS. RESULTS: Twenty-nine women (52%) had optimal cytoreduction (OC), and 27 (48%) had suboptimal cytoreduction (SC). Women in the SC group had higher median CA-125 values at surgery (954 SC vs 597 OC, P = .07). Three sites of disease on preoperative CT were reported more frequently in the SC patients; omentum (P = .007), parietal peritoneum (P = .096), and ascites (P = .093). CONCLUSION: A suboptimal cytoreduction confers no survival advantage to women with advanced ovarian cancer. Thus, these patients may be the best candidates for initial chemotherapy, and identifying them preoperatively becomes important.

Genomic organization, incidence, and localization of the SPAN-x family of cancer-testis antigens in melanoma tumors and cell lines.

PURPOSE: Members of the SPAN-X (sperm protein associated with the nucleus mapped to the X chromosome) family of cancer-testis antigens are promising targets for tumor immunotherapy because they are normally expressed exclusively during spermiogenesis on the adluminal side of the blood-testis barrier, an immune privileged compartment. EXPERIMENTAL DESIGN AND RESULTS: This study analyzed the human SPANX genomic organization, as well as SPAN-X mRNA and protein expression in somatic and cancer cells. The SPANX family consists of five genes, one of which is duplicated, all located in a gene cluster at Xq27.1. From the centromere, the arrangement of the five SPANX genes mapped on one contiguous sequence is SPANXB, -C, -A1, -A2, and -D. Reverse transcription-PCR analyses demonstrated expression of SPAN-X mRNA in melanoma and ovarian cell lines, and virtual Northern analysis established SPANX gene expression in numerous cancer cell lines. Immunoblot analysis using polyclonal antisera raised against recombinant SPAN-X confirmed the translation of SPAN-X proteins in melanoma and ovarian tumor cell lines. The immunoreactive proteins migrated between M(r) 15,000 and M(r) 20,000 similar to those observed in spermatozoa. Immunoperoxidase labeling of melanoma cells and tissue sections demonstrated SPAN-X protein localization in the nucleus, cytoplasm, or both. Ultrastructurally, in melanoma cells with nuclear SPAN-X, the protein was associated with the nuclear envelope, a localization similar to that observed in human spermatids and spermatozoa. Significantly, the incidence of SPAN-X-positive immunostaining was greatest in the more aggressive skin tumors, particularly in distant, nonlymphatic metastatic melanomas. CONCLUSIONS: The data herein suggest that the SPAN-X protein may be a useful target in cancer immunotherapy.

Sentinel node biopsy in vulvar and vaginal melanoma: presentation of six cases and a literature review.

BACKGROUND: Urogenital melanoma is a rare neoplasm with poor prognosis. Its management in the past involved radical vulvectomy and complete bilateral inguinofemoral lymphadenectomy. Sentinel lymph node biopsy is an accurate low-morbidity procedure when used in the context of cutaneous melanoma. However, prophylactic lymphadenectomy has not been shown to improve survival of melanoma patients. We wanted to determine the feasibility of sentinel lymph node biopsy in patients with female urogenital melanoma as a staging procedure. METHODS: Six patients with vulvar or vaginal melanomas underwent preoperative lymphatic mapping with (99m)Tc-labeled sulfur colloid followed by sentinel lymphadenectomy. In addition, we reviewed the literature on the application of sentinel lymph node biopsy in urogenital tract melanomas. RESULTS: One or more sentinel nodes were identified in all six patients by lymphoscintigraphy. All patients underwent sentinel lymphadenectomy, except for one patient with a deep vaginal melanoma that drained to pelvic nodes. The five successful cases had unilateral drainage patterns. None of the sentinel lymph nodes excised had tumor invasion. Combined with five other patients from the published literature, the success rate of localizing sentinel lymph nodes in the patients with urogenital melanoma approaches 100%. CONCLUSIONS: This experience, plus reports of a small number of patients from three similar studies, supports the impression that sentinel lymph node biopsy is feasible for vulvar and vaginal melanoma.

"See-and-treat" loop electrosurgical excision. Has the time come for a reassessment?

OBJECTIVE: To review the results of a policy decision to offer selected women with cervical high grade squamous intraepithelial lesions (HSILs) loop electrosurgical excision (LEEP) at the time of their initial colposcopic evaluation. STUDY DESIGN: Sixty-one patients with newly diagnosed cytologic cervical HSIL were evaluated for inclusion in a "see-and-treat" protocol. Fifty of these patients met inclusion criteria and underwent immediate loop excision of the cervical transformation zone at their initial colposcopic visit. RESULTS: Forty-eight of 50 patients that underwent see-and-treat management at their initial colposcopic evaluation had histologic evidence of cervical dysplasia/neoplasia. The positive predictive value of diagnostic colposcopy in this setting was 96%, with a 95% confidence interval (88-99%). Two patients had no pathologic abnormality, for an overtreatment incidence of 4%. CONCLUSION: The selected use of see-and-treat management of cytologic cervical HSIL is feasible, highly predictive and associated with an extremely low incidence of overtreatment. Such management has the potential to increase patient satisfaction and compliance while drastically reducing health care dollars currently directed toward the management of HSIL. Strong consideration should be given to accepting see-and-treat management as a viable alternative in the care of patients with documented cervical cytologic HSIL.

Advances in the management of endometrial adenocarcinoma. A review.

Endometrial adenocarcinoma is the most common and curable gynecologic neoplasm; the five-year survival for women with surgical stage I disease ranges from 83% to 93%; stage II, 73%; stage III, 52%; and stage IV, 27%. The absence of an asymptomatic latency phase amenable to detection through screening and the already excellent cure rates seen with early-stage disease have precluded the need for endometrial cancer screening programs. Adenocarcinomas constitute 97% of endometrial cancers, with endometrioid the most common histologic subtype. Two different pathways of endometrial carcinogenesis exist. One arises in a background of estrogen excess, giving rise to atypical hyperplasia as the malignant precursor of the more common endometrioid adenocarcinomas. The use of oral contraceptives has consistently been shown to decrease the risk of developing endometrial carcinoma via this pathway, with 12 months or more of continuous use decreasing the lifetime risk by 40-50%. The alternate pathway of endometrial carcinogenesis represents malignant transformation of atrophic endometrium and proceeds through endometrial intraepithelial carcinoma as the malignant precursor of the more virulent serous papillary and clear cell endometrial adenocarcinomas. The staging of endometrial cancer (according to the International Federation of Obstetrics and Gynecology) is surgical. Recent studies suggest a therapeutic benefit associated with extensive retroperitoneal lymph node evaluation to determine the disease extent and thereby more effectively direct potentially life-saving adjuvant therapy. Adjuvant radiation therapy, known to have survival benefit in advanced-stage disease, may also have survival benefit in intermediate-risk surgical stage I disease on the basis of results recently released from a Gynecologic Oncology Group study. The use of radiation therapy, systemic chemotherapy and hormonal therapy, alone or in combination, is recommended for primary advanced and recurrent disease.