Ovarian cancer causes more deaths than any other cancer of the female genital tract. Despite improvements in management and treatment, survival remains low in patients with extensive disease at ...presentation, which usually leads to eventual recurrence. Treatment of recurrence remains challenging. Although the use of secondary cytoreduction to treat recurrent disease has become widespread, its utility remains unproven.
This systematic review examines all the relevant electronic literature. An electronic literature search was conducted in the PubMed, MEDLINE, and EMBASE databases from January 1980 through December 2019.
Several relevant retrospective studies have been published, and these unanimously suggest that secondary cytoreduction is associated with an increase in progression-free and overall survival after relapse. Despite sound statistical methods, these studies are unfortunately limited by significant confounding inherent to the retrospective approach and by selection bias, given that healthier patients with less disease have historically been selected for surgery. Data from clinical trials are currently evolving. Early data from DESKTOP III demonstrate improved progression-free survival with secondary cytoreduction, whereas GOG-0213 found no difference in progression-free or overall survival.
Secondary cytoreduction remains a viable treatment option for select patients for now, but this is entirely dependent on the highly anticipated overall survival results of DESKTOP III and SOC 1.
Objective We examined the effect of radiation on survival for early-stage uterine carcinosarcomas and leiomyosarcomas. Study Design The surveillance, epidemiology, and end results database was used ...to identify patients with stage I/II carcinosarcomas and leiomyosarcomas. Logistic regression and Cox models were developed to determine radiation use and survival. Results Among 1819 women with carcinosarcomas and 1088 women with leiomyosarcomas, radiation was administered to 667 of the patients (37%) with carcinosarcomas and to 235 of the patients (22%) with leiomyosarcomas. In a multivariate model, adjuvant radiation reduced the risk of death by 21% in women with carcinosarcomas (hazard ratio, 0.79; 95% CI, 0.7-0.9). Radiation reduced mortality rates in patients with carcinosarcomas who had not undergone node dissection but had only a marginal effect on survival in node-negative women. Adjuvant radiation had no effect on survival for early-stage leiomyosarcomas (hazard ratio, 1.1; 95% CI, 0.9-1.4). Conclusion Adjuvant radiotherapy improves survival for select patients with early-stage carcinosarcomas but is of limited value for leiomyosarcomas.
Surgery and chemotherapy form the cornerstone of the treatment for ovarian cancer. Currently, the standard of care for primary ovarian cancer is platinum and taxane-based therapy. Even among women ...with advanced and suboptimal disease (i.e. tumors greater than 1 cm) following surgery, the clinical efficacy of chemotherapy is noteworthy. Despite the favorable response characteristics, however, most women with advanced-stage ovarian cancer will relapse, including about 50% of women who have no evidence of disease after primary therapy. A multitude of treatment options are available at the time of recurrence, but there is no clear consensus about how these patients should be managed. Options include surgery, chemotherapy, hormones, and sometimes, radiation therapy. The sequence, combinations of treatment, and manner in which any or all of these options should be employed in an individual patient, which heretofore have not been standardized, are the subjects of ongoing clinical investigations.
Staying current on the rapidly evolving therapeutic landscape in oncology is challenging for clinicians. This commentary discusses exciting practice‐changing data specific to ovarian cancer.
To determine the relationship between chemotherapy dose modification (dose adjustment or treatment delay), overall survival (OS) and progression-free survival (PFS) for women with advanced-stage ...epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma (PPC) who receive carboplatin and paclitaxel.
Women with stages III and IV EOC and PPC treated on the Gynecologic Oncology Group phase III trial, protocol 182, who completed eight cycles of carboplatin with paclitaxel were evaluated in this study. The patients were grouped per dose modification and use of granulocyte colony stimulating factor (G-CSF). The primary end point was OS; Hazard ratios (HR) for PFS and OS were calculated for patients who completed eight cycles of chemotherapy. Patients without dose modification were the referent group. All statistical analyses were performed using the R programming language and environment.
A total of 738 patients were included in this study; 229 (31%) required dose modification, 509 did not. The two groups were well-balanced for demographic and prognostic factors. The adjusted hazard ratios (HR) for disease progression and death among dose-modified patients were: 1.43 (95% CI, 1.19–1.72, P < 0.001) and 1.26 (95% CI, 1.04–1.54, P = 0.021), respectively. Use of G-CSF was more frequent in dose-modified patients with an odds ratio (OR) of 3.63 (95% CI: 2.51–5.26, P < 0.001) compared to dose-unmodified patients.
Dose-modified patients were at a higher risk of disease progression and death. The need for chemotherapy dose modification may identify patients at greater risk for adverse outcomes in advanced stage EOC and PPC.
•Chemotherapy dose modification is common in ovarian cancer treatment.•Patients requiring dose modification are more likely to require growth factor.•Dose modified patients are at a higher risk of worse treatment outcome.
Objective.
The objective of this study was to evaluate a cost‐effectiveness strategy of bevacizumab in a subset of high‐risk advanced ovarian cancer patients with survival benefit.
Methods.
A subset ...analysis of the International Collaboration on Ovarian Neoplasms 7 trial showed that additions of bevacizumab (B) and maintenance bevacizumab (mB) to paclitaxel (P) and carboplatin (C) improved the overall survival (OS) of high‐risk advanced cancer patients. Actual and estimated costs of treatment were determined from Medicare payment. Incremental cost‐effectiveness ratio per life‐year saved was established.
Results.
The estimated cost of PC is $535 per cycle; PCB + mB (7.5 mg/kg) is $3,760 per cycle for the first 6 cycles and then $3,225 per cycle for 12 mB cycles. Of 465 high‐risk stage IIIC (>1 cm residual) or stage IV patients, the previously reported OS after PC was 28.8 months versus 36.6 months in those who underwent PCB + mB. With an estimated 8‐month improvement in OS, the incremental cost‐effectiveness ratio of B was $167,771 per life‐year saved.
Conclusion.
In this clinically relevant subset of women with high‐risk advanced ovarian cancer with overall survival benefit after bevacizumab, our economic model suggests that the incremental cost of bevacizumab was approximately $170,000.
摘要
目的 本研究的目的是在一个获得生存益处的高危晚期卵巢癌患者亚组中，对贝伐单抗治疗的一项成本效益策略进行评估。
方法 对国际协作组卵巢肿瘤 7 试验进行的一项亚组分析表明，在紫杉醇 (P) 和卡铂 (C) 的基础上添加贝伐单抗 (B) 和延用贝伐单抗 (mB) 可延长高危晚期癌症患者的总生存期 (OS)。我们根据 Medicare 付款情况确定了实际治疗成本和估计治疗成本， 并确立了每拯救一个寿命年所对应的成本效益增量比值。
结果 PC 的估计成本为每周期 535 美元；PCB + mB (7.5 mg/kg) 的估计成本在前 6 个周期内为每周期 3,760 美元，在后 12 个 mB 周期内为每周期 3,225 美元。在 465 名高危 III 期（残留灶 >1 cm）或 IV 期患者中，既往报告的 PC 后 OS 为 28.8 个月，而那些接受 PCB + mB 之患者的 OS 则为 36.6 个月。在 OS 估计延长 8 个月的情况下，由 B 导致的成本效益增加比率为每拯救一个寿命年即增加 167,771 美元成本。
结论 在这个使用贝伐单抗后获得生存益处的临床重要高危晚期卵巢癌女性亚组中，我们的经济模型表明，由贝伐单抗导致的成本增加值约为 170,000 美元。The Oncologist 2014;19:523–527
The financial burden of cancer care has more than doubled in the past decade. The use of bevacizumab for ovarian cancer has not been shown to be cost‐effective. In this economic analysis in a subset of high‐risk advanced ovarian cancer patients with survival benefit, we showed that adding bevacizumab was near cost‐effective based on current benchmarks. With limited health care resources, future clinical trials should incorporate a prospective collection of costs, long‐term treatment toxicity, and quality of life.
To explore safety and tolerability parameters for the niraparib individualized starting dose (ISD) in patients with newly diagnosed advanced ovarian cancer that responded to platinum-based ...chemotherapy who participated in the phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016).
The PRIMA protocol was amended so newly enrolled patients received an ISD based on baseline body weight/platelet count. In this ad hoc analysis, the timing, duration, and resolution of the first occurrence of common any-grade hematologic (thrombocytopenia, anemia, neutropenia) and nonhematologic (nausea, asthenia/fatigue, constipation, insomnia, hypertension) treatment-emergent adverse events (TEAEs) were evaluated by treatment arm in the ISD safety population (data cutoff, November 17, 2021; median follow-up, 3.5 years).
Of 733 randomized patients, 255 were enrolled after the ISD protocol amendment and received ≥ 1 dose of study treatment (niraparib, 169; placebo, 86). In the niraparib arm, median times to first events were 22.0–35.0 days for hematologic TEAEs and 7.0–56.0 days for nonhematologic TEAEs. First events resolved in ≥ 89.8% of patients for hematologic TEAEs; for nonhematologic TEAEs, resolution rates ranged from 55.3% (insomnia) to 86.0% (nausea). Median durations of first hematologic TEAEs were ≤ 16.0 days, but for first nonhematologic TEAEs ranged from 18.0 days (nausea) to 134.0 days (insomnia).
The niraparib ISD was generally well tolerated and TEAEs were manageable. Common hematologic and nonhematologic TEAEs occurred early and first events of hematologic TEAEs had a short duration (≈ 2 weeks) and a high resolution rate. These findings support close monitoring immediately following niraparib initiation and may help inform patient expectations for niraparib safety.
Display omitted
•Tolerability of niraparib individualized starting dose (ISD) in PRIMA/ENGOT-OV26/GOG-3012.•Evaluated timing, duration, and resolution of first occurrence of common TEAEs.•Hematologic and nonhematologic TEAEs occurred early after niraparib ISD treatment initiation.•First events of hematologic TEAEs had short durations and high rates of resolution.•Niraparib ISD was well tolerated, and common TEAEs were generally manageable.
Persistent HPV16 infection is a major cause of the global cancer burden. The viral life cycle is dependent on the differentiation program of stratified squamous epithelium, but the landscape of ...keratinocyte subpopulations which support distinct phases of the viral life cycle has yet to be elucidated. Here, single cell RNA sequencing of HPV16 infected compared to uninfected organoids identifies twelve distinct keratinocyte populations, with a subset mapped to reconstruct their respective 3D geography in stratified squamous epithelium. Instead of conventional terminally differentiated cells, an HPV-reprogrammed keratinocyte subpopulation (HIDDEN cells) forms the surface compartment and requires overexpression of the ELF3/ESE-1 transcription factor. HIDDEN cells are detected throughout stages of human carcinogenesis including primary human cervical intraepithelial neoplasias and HPV positive head and neck cancers, and a possible role in promoting viral carcinogenesis is supported by TCGA analyses. Single cell transcriptome information on HPV-infected versus uninfected epithelium will enable broader studies of the role of individual keratinocyte subpopulations in tumor virus infection and cancer evolution.
To describe trends in and predictors of surgical mesh use for pelvic organ prolapse (POP) repair and to estimate the influence of safety advisories on mesh use.
Analysis of women aged 18 years and ...older recorded in a health care quality and resource utilization database who underwent POP repair from 2000 to 2010, identified by International Classification of Diseases, 9th Revision, Clinical Modification procedure codes, and stratified by mesh use. Odds ratios were calculated with adjustments for patient, physician, and hospital-level characteristics.
Among 273,275 women in the cohort, 64,968 (23.8%) underwent a mesh-augmented repair. Concurrent incontinence surgery was a strong predictor of mesh use (odds ratio OR 9.95; 95% confidence interval CI 9.70-10.21). Mesh use increased from 7.9% in 2000 to a peak of 32.1% in 2006, and declined slightly to 27.5% in 2010. Among women without incontinence, mesh use increased from 3.3% in 2000 to 13.5% in 2006, and remained stable at 12.8% in 2010. Intermediate-volume (OR 1.53; 95% CI 1.44-1.62) and high-volume (OR 2.74; 95% CI 2.58-2.92) surgeons were more likely to use mesh than low-volume surgeons. Compared with women who underwent operation by gynecologists, those treated by urologists were more than three times more likely to undergo mesh-augmented prolapse repair (OR 3.36; 95% CI 3.09-3.66). Black women were 27% less likely to undergo mesh repair (OR 0.73; 95% CI 0.66-0.82).
Mesh-augmented prolapse repairs increased substantially over the past decade, and this increase was most pronounced in the years before the publication of safety advisories. Physician specialty and surgical volume are important factors underlying mesh use. Additional measures must ensure evidence-based use of mesh for pelvic reconstruction.
II.
Abstract Purpose A simple measure to predict chemotherapy tolerance in elderly patients would be useful. We prospectively tested the association of baseline Instrumental Activities of Daily Living ...(IADL) score with ability to complete 4 cycles of first line chemotherapy without dose reductions or > 7 days delay in elderly ovarian cancer patients. Patients and methods Patients' age ≥ 70 along with their physicians chose between two regimens: CP (Carboplatin AUC 5, Paclitaxel 135 mg/m2 ) or C (Carboplatin AUC 5), both given every 3 weeks either after primary surgery or as neoadjuvant chemotherapy (NACT) with IADL and quality of life assessments performed at baseline, pre-cycle 3, and post-cycle 4. Results Two-hundred-twelve women were enrolled, 152 selecting CP and 60 selecting C. Those who selected CP had higher baseline IADL scores (p < 0.001). After adjusting for age and PS, baseline IADL was independently associated with the choice of regimen (p = 0.035). The baseline IADL score was not found to be associated with completion of 4 cycles of chemotherapy without dose reduction or delays (p = 0.21), but was associated with completion of 4 cycles of chemotherapy regardless of dose reduction and delay (p = 0.008) and toxicity, with the odds ratio (OR) of grade 3 + toxicity decreasing 17% (OR: 0.83; 95%CI: 0.72–0.96; p = 0.013) for each additional activity in which the patient was independent. After adjustment for chemotherapy regimen, IADL was also associated with overall survival (p = 0.019) for patients receiving CP. Conclusion Patients with a higher baseline IADL score (more independent) were more likely to complete 4 cycles of chemotherapy and less likely to experience grade 3 or higher toxicity.
PDF
