Immunotherapy of gynecological cancers

Oncology treatments have evolved from intuitive, via empiric, to the present precision medicine, with the integration of molecular targeted therapies in our treatment arsenal. The use of the patients’ powerful immune system has long been contemplated and recently led to the integration of immunotherapy to overturn the well-documented inhibitory effects of the tumor on the immune system and restore it to a state of activity against the cancer. Recent favorable results have shown the value and effectiveness of immunotherapy against gynecological cancers. In particular, the checkpoint inhibitors, targeting the programmed death-1 (PD-1) pathway, have shown durable clinical responses with manageable toxicity. Several phase II and III clinical trials testing the association of different regimen of chemotherapy and immunotherapy are ongoing in gynecological cancers, and important results are expected. In this chapter, we outline the main principles of immunotherapy for gynecological cancers and summarize the current strategies used in clinical trials.     

Clinical picture of women with early stage ovarian cancer

OBJECTIVE: The objective of this study was to review the clinical picture of women with early stage ovarian cancer, to examine the difference between women with borderline ovarian tumors (BLOT) and those with ovarian cancer (OC), and to estimate the average time interval between the onset of symptoms and diagnosis. METHODS: A retrospective review of all women with surgical stage I and II OC or BLOT was performed and the following information abstracted: age, parity, family history of cancer, personal history of previous malignancies, symptoms, signs, date of start of symptoms, imaging studies, CA-125 values, date of diagnosis at surgery, tumor stage, histology, grade, date of last follow-up, and condition at last follow-up. Comparison between patients with BLOT and OC was performed using chi(2) and two-sample t tests. RESULTS: Our search identified 72 women with surgical stage I and II BLOT (n = 22) or OC (n = 50). Seventy-eight percent of the patients had presenting symptoms, the most common of which were abdominal or pelvic pain (34. 7%), bloatedness (31.9%), and vaginal bleeding (19.4%). Symptoms were similar among women with BLOT and those with OC, with a higher proportion of BLOT patients reporting no symptoms (31.8% versus 18. 0%, respectively). Abdominal and/or pelvic masses were palpable in 72.2% of the patients and ascites was present in 12.5%. Ovarian masses were most commonly complex in appearance and CA-125 was elevated in 52.2% of the patients in whom CA-125 values were known. The average time interval between onset of symptoms and diagnosis was 4.6 months (range 0.1-24.4 months). Women with BLOT had a significantly longer average time interval than women with OC (8.0 +/- 7.7 versus 3.4 +/- 3.7 months, respectively, P = 0.03). CONCLUSIONS: The majority of women with early stage ovarian cancer have nonspecific symptoms. The array of symptoms is similar between women with BLOT and those with OC. However, women with BLOT tend to have a longer time interval from onset of symptoms to diagnosis.     

Use of complementary and alternative medicine among women with gynecologic cancers

OBJECTIVE: The aim of this study was to determine the prevalence and types of complementary and alternative medicine (CAM) usage by women with gynecologic cancer in an outpatient midwestern university practice. METHODS: Any patient with a gynecologic cancer seen in the outpatient clinic of the gynecologic oncology division at Washington University over a 3-month period was eligible, excluding those patients with a new cancer diagnosis. Subjects completed a questionnaire anonymously. Two by two comparisons were made using the Fisher exact test and P was considered significant at P < 0.05. RESULTS: Nearly half (49.6%) of 113 respondents had used CAM since being diagnosed with cancer. Characteristics significantly associated with CAM use include annual income greater than $30,000, cancer site of origin other than the cervix, and use of CAM prior to cancer diagnosis. Users with annual incomes greater than $30,000 were significantly more likely to use CAM in the "other" category that included acupuncture, reflexology, and electromagnetic therapy. Fewer than 25% of CAM users received information regarding CAM from a physician, nurse, or practitioner of CAM. Women used CAM in hopes of achieving a wide range of potential benefits including both improved well-being and anti-cancer effects. The most common actual benefit these women perceived was an improvement in psychosocial well-being, including increased hope or optimism. CONCLUSIONS: American patients with gynecologic cancer frequently use CAM in addition to standard medical therapy. Oncologists caring for women with gynecologic cancer should initiate a dialogue about usage of CAM, discussing the potential adverse effects of CAM and the patient's therapeutic goals.     

Quality of life and gynecological cancers

The quality of life is becoming more and more important for women after demolitive surgery for genital malignancies. A sample of 58 cases of genital malignancies are compared with 50 cases of benign neoplasms (fibroids) and their effects on sexuality, as a parameter of the quality of life, are studied and reported.     

The experience of long-term hospital follow-up for women who have suffered early stage gynecological cancer: a qualitative interview study

Abstract. Bradley EJ, Pitts MK, Redman CWE, Calvert E. The experience of long term hospital follow-up for women who have suffered early stage gynecological cancer: a qualitative interview study.
The objective of this paper is to investigate the factors involved in the wish for continuing long-term follow-up for early stage gynecological cancer in the absence of obvious clinical benefit. This qualitative study is comprised of semistructured, individual interviews.
Twelve women who had been treated for early stage (I-II) gynecological cancer (cervical, vulval, ovarian, endometrial) and had been attending regular follow-up appointments at the hospital clinic for a minimum of six months were interviewed for this study. The primary outcome measures were women's views on their follow-up needs.
Women who continue to express a need for follow-up appointments years after the treatment of active disease are seeking to alleviate anxiety regarding possible recurrent illness. The main element of follow-up that alleviates this recurrence anxiety is medical reassurance, this is only judged to be worthwhile when given by a gynecological consultant. There is a difficulty with regarding the period of remission as a healthy state, both cultural lay beliefs and family support exacerbate this difficulty. Although family support is deemed important initially, it may actually serve to maintain sickness identity, perpetuating views of cancer remission as another stage of illness.
We conclude that the processes involved in follow-up for cancers with a very low recurrence risk are complex. Follow-up information is perhaps medical, but women who have a continued need for follow-up in the absence of any clinical disease are attending for psychological purposes. Further research is needed to study possible interventions that could be introduced to help alleviate anxiety during the period of cancer recovery.     

Detection of disseminated tumor cells in patients with gynecological cancers

OBJECTIVES: The presence of disseminated tumor cells (DTC) in breast cancer patients is associated with poor prognosis. However, there are limited data about the prevalence and prognostic impact of DTC in patients with gynecological tumors. The aim of this study was to evaluate the presence of DTC in the bone marrow (BM) of patients with gynecological cancers and to correlate their presence with established prognostic factors. METHODS: BM aspirates of 201 patients with primary ovarian (n=69), cervical (n=54) and endometrial cancer (n=78), undergoing surgery at the Department of Gynecology and Obstetrics, University Hospital, Tuebingen, Germany between 1/2002 and 01/2006, were included into the study. Cytokeratin (CK)-positive cells were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3. RESULTS: The bone marrow positivity rate was 36% in ovarian, 26% in cervical and 17% in endometrial cancer, respectively. Presence of DTC was significantly correlated with FIGO (International Federation of Gynecology and Obstetrics) tumor stage (p<0.05). The recurrence rate was 14% in patients with CK-positive cells compared to 8% in CK-negative patients (p=0.2). There was no correlation between DTC and other established prognostic factors including nodal status or grading except for cervical cancer. Patients with positive lymph node status were more likely to be bone marrow positive compared to those with negative lymph node status (p<0.05). CONCLUSIONS: Disseminated tumor cells seem to be a general phenomenon in epithelial tumors even though their clinical impact remains to be evaluated. The hypothesis that bone marrow is the homing site of disseminated tumor cells is further supported by these data since gynecological tumors only rarely metastasize to the skeletal system.     

Postpartum health among rural Zambian women

Health problems after childbirth have received little attention compared to maternal morbidity in the antenatal period and during labour. We conducted a hospital-based study to investigate postpartum health problems in rural Zambian women. Health problems are very common: 84% of the 620 study participants reported at least one health problem. The majority of women who experienced a health problem took action to relieve the complaint. High vaginal swabs were used to diagnose a genital tract infection. Seventeen per cent of the swabs were abnormal; most women with abnormal result showed no symptoms of genital tract infection. Ninety three per cent of women with symptoms suggestive of a genital tract infection did not seek medical attention. Further research is needed to estimate the impact of self-reported health problems on women's daily lives. Women should be educated on specific conditions that require medical care. More information is also needed on the prevalence of sexually transmitted infections in antenatal and postpartum women including the feasibility of mass screening and treatment in this group of women.     

Prediction of delivery among women with early preterm labor by means of clinical characteristics alone

OBJECTIVE: This study was undertaken to assess whether individual clinical factors or combinations thereof could be used to accurately predict the risk of delivery within 1 week of admission among women with preterm labor and minimal cervical dilatation. STUDY DESIGN: We performed a case-control study of patients admitted to our institution with preterm labor and minimal cervical dilatation. A case patient was a patient who sought treatment with uterine contractions between 24 and 34 weeks' gestation with cervical dilatation 70 potential predictors was recorded. Statistical analysis consisted of bivariate and multivariable methods. We also generated a multivariable clinical predictive model with the purpose of detecting a proportion as high as possible of those destined to be delivered within 1 week (high sensitivity). We estimated that we would need 50 case patients and 150 control subjects to detect an odds ratio of 2.5 for risk factors with a prevalence of 20%, an alpha error of.05, a beta error of.20, and a control subject/case patient ratio of 3:1. RESULTS: Three variables were eligible for inclusion in our logistic models according to the bivariate analyses-bleeding on admission, substance abuse, and admission white blood cell count >/=14,000 cells/microL. The simplest and most favorable model included only 2 variables, bleeding and substance abuse, and yielded a sensitivity of 46% and a specificity of 76%. The full 3-variable model had similar test characteristics. For no model were we able to achieve a sensitivity >/=50%. CONCLUSION: The results of this case-control study suggest that combinations of clinical factors do not yield an adequate level of discrimination to be used alone for predicting the likelihood of delivery within 1 week among patients with minimal degrees of cervical dilatation.     

妊娠合并妇科恶性肿瘤的诊治

<正>妊娠合并妇科恶性肿瘤较少见。据美国的统计数据,妊娠合并恶性肿瘤发生率约3.3/万,依次为乳腺癌、甲状腺癌、子宫颈癌、何杰金病及卵巢癌[1]。国内缺乏大样本的统计数据。妊娠合并妇科恶性肿瘤的治疗应结合肿瘤性质、临床期别、孕周、患者及家属对胎儿的考虑等因素综合考虑,现就上述问题总数如下。一、妊娠合并宫颈癌关于妊娠合并宫颈癌目前尚缺乏统一的定义,多数学者认为,妊娠期与产后6个月内发现的宫颈癌与非妊娠宫颈癌有所不同,建议将其命名为妊娠相关性宫颈癌。宫颈癌     

分子靶向治疗药物在妇科肿瘤中的研究进展

分子靶向治疗是以肿瘤细胞的特性改变为作用靶点,在发挥抗肿瘤活性的同时,减少对正常细胞的不良反应.近年此类药物在临床实践中取得显著疗效,其有的放矢的治疗方法将妇科肿瘤治疗推向了新阶段.分别对针对表皮生长因子受体家族、以血管生成为靶点的分子靶向治疗以及环氧合酶抑制剂等4种靶向治疗药物在子宫肌瘤、外阴癌、宫颈癌、子宫内膜癌、子宫肉瘤、卵巢癌中的研究现状、应用前景进行总结及展望.     

宫颈癌根治术中行卵巢移位的临床效果分析

目的探讨宫颈癌根治术中行卵巢移位术术后卵巢的功能状况。方法1999年1月至2003年12月江门市新会区人民医院等2家医院收治43例年龄26~40岁宫颈癌ⅠB~ⅡA期患者,其中22例在宫颈癌根治术中行卵巢移位术为观察组,21例行传统的宫颈癌根治术为对照组。术后应用血FSH、LH、E2及Kuppermann评分进行卵巢功能测定,随访1~4年。结果观察组术后4年内卵巢功能基本正常,对照组术后1个月卵巢功能丧失。两组记录生存质量的改良Kuppermann评分比较差异有非常显著性意义(P<0·01),而复发率和存活率比较差异无显著性意义(P>0·05)。结论宫颈癌患者在宫颈癌根治术时行卵巢移位术,可保留卵巢功能。     

Complications of combined radical hysterectomy-postoperative radiation therapy in women with early stage cervical cancer

Fifty patients with cervical cancer were treated with radical hysterectomy and lymphadenectomy followed by postoperative radiation therapy for high risk factors (nodal metastases, lymphvascular space invasion, close or involved margins) at the University of Alabama at Birmingham Medical Center from 1969 to 1984. Fifteen (30%) of the patients treated had serious complications, 8 (16%) requiring an operation, and 1 (2%) dying as a result of treatment-related problems. This combined modality approach is associated with significant complications.     

Application of sentinel lymph node dissection in gynecological cancers: results of a survey among German hospitals

Purpose

Evaluating the application of the sentinel lymph node dissection (SLND) in gynecological cancers among German hospitals.

Methods

Between March and June 2016 an online questionnaire on SLND in gynecologic cancers was sent by email to all German gynecologic cancer centers, all university hospitals and general hospitals for which an email address was available. The survey contained 61 questions regarding the SLND in vulvar, cervical, endometrial and ovarian cancer.

Results

In total, 63 clinics, including 13 (20.6%) university hospitals, 28 (44.4%) hospitals offering maximum care and 22 (34.9%) general hospitals, responded to the questionnaire. Most clinics (46/63, 73%) performed SLND in vulvar cancer with a median amount of 7.8 (range 1–43) SLND per year. 56.5% of the clinics included patients according to the German national guidelines and performed ultrastaging of negative SLN. Furthermore, 18/63 (28.5%) of the responding clinics applied SLND in cervical cancer including 7 (77.8%) centers which conducted isolated SLND without radical pelvic lymph node dissection (LND). Preoperative imaging with planar lymphoscintigraphy (LSG) was applied in 12/18 (66.7%) of the clinics. SLND in endometrial cancer was reported by 4/63 (6.4%) hospitals. Three of them (75%) regularly performed a subsequent radical pelvic LND. One clinic (1.5%) reported SLND in ovarian cancer in combination with radical LND.

Conclusion

Especially in vulvar and cervical cancer, isolated SLND appears to be partially implemented in the routine surgical treatment. However, this survey illustrates a wide heterogeneity regarding inclusion criteria and application of the SLND approach.

     

Sexual outcomes following treatment for early stage gynecological cancer: a prospective multicenter study

Abstract. Kylstra WA, Leenhouts GHMW, Everaerd W, Panneman MJM, Hahn DEE, Weijmar Schultz WCM, van de Wiel HBM, Heintz APM. Sexual outcomes following treatment for early-stage gynecological cancer: a prospective multicenter study.
Data are presented of a prospective, longitudinal study on the impact of early stage gynecological cancer on sexuality. Women with a partner ( n = 58) completed self-report questionnaires following diagnosis but prior to treatment and then at 6 and 12 months post-treatment. A single assessment was also obtained from a healthy comparison group ( n = 103). Pre-treatment cancer patients reported fewer and less trouble with sexual problems compared to healthy controls. Neither sexual satisfaction nor sexual activity changed from pre- to post-treatment and was comparable to that of healthy controls. Post-treatment, relatively minor sexual difficulties were shown; a notable difficulty for cancer patients concerned lubrication. At 12 months post-treatment, the sexual functioning of cancer patients was comparable to healthy controls.