論文

Gynecologic melanomas are rare and have a poor prognosis. Although immunotherapy (immune checkpoint inhibitors) and targeted therapy has greatly improved the systemic treatment of cutaneous melanoma (CM) in recent years, its efficacy in gynecologic melanomas remains uncertain because of the rarity of this malignancy and its scarce literature. This review aimed to evaluate the literature of gynecologic melanomas treated with immunotherapy and targeted therapy through a PubMed search. We identified one study focusing on the overall survival of gynecologic melanomas separately and five case series and nine case reports concentrating on gynecologic melanomas treated with an immune checkpoint inhibitor and/or targeted therapy. Furthermore, the KIT mutation has the highest rate among all mutations in mucosal melanoma types. The KIT inhibitors (Tyrosine kinase inhibitors: TKIs) imatinib and nilotinib could be the treatment options. Moreover, immune checkpoint inhibitors combined with KIT inhibitors may potentially treat cases of resistance to immune checkpoint inhibitors. However, because of the different conditions and a small number of cases, it is difficult to evaluate the efficacy of immunotherapy and targeted therapy for gynecologic melanoma rigorously at this time. Further prospective cohort or randomized trials of gynecologic melanoma alone are needed to assess the treatment with solid evidence.

Many efforts are underway to develop novel therapies against the aggressive high-grade serous ovarian cancers (HGSOCs), while our understanding of treatment options for low-grade (LGSOC) or mucinous (MUCOC) of ovarian malignancies is not developing as well. We describe here a functional precision oncology (fPO) strategy in epithelial ovarian cancers (EOC), which involves high-throughput drug testing of patient-derived ovarian cancer cells (PDCs) with a library of 526 oncology drugs, combined with genomic and transcriptomic profiling. HGSOC, LGSOC and MUCOC PDCs had statistically different overall drug response profiles, with LGSOCs responding better to targeted inhibitors than HGSOCs. We identified several subtype-specific drug responses, such as LGSOC PDCs showing high sensitivity to MDM2, ERBB2/EGFR inhibitors, MUCOC PDCs to MEK inhibitors, whereas HGSOCs showed strongest effects with CHK1 inhibitors and SMAC mimetics. We also explored several drug combinations and found that the dual inhibition of MEK and SHP2 was synergistic in MAPK-driven EOCs. We describe a clinical case study, where real-time fPO analysis of samples from a patient with metastatic, chemorefractory LGSOC with a CLU-NRG1 fusion guided clinical therapy selection. fPO-tailored therapy with afatinib, followed by trastuzumab and pertuzumab, successfully reduced tumour burden and blocked disease progression over a five-year period. In summary, fPO is a powerful approach for the identification of systematic drug response differences across EOC subtypes, as well as to highlight patient-specific drug regimens that could help to optimise therapies to individual patients in the future.

Background: Concurrent chemoradiotherapy has been the standard of care for locally advanced cervical cancer for over 20 years; however, 30–40% of treated patients have recurrence or progression within 5 years. Immune checkpoint inhibition has improved outcomes for patients with PD-L1 positive metastatic or recurrent cervical cancer. We assessed the benefit of adding durvalumab, a PD-L1 antibody, with and following chemoradiotherapy for locally advanced cervical cancer. Methods: The CALLA randomised, double-blind, phase 3 trial included 105 hospitals across 15 countries. Patients aged at least 18 years with previously untreated locally advanced cervical cancer (adenocarcinoma, squamous, or adenosquamous; International Federation of Gynaecology and Obstetrics [FIGO] 2009 stage IB2–IIB lymph node positive, stage ≥III any lymph node status) and WHO or Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) through an interactive web response system using a permuted block size of 4 to receive durvalumab (1500 mg intravenously once every 4 weeks) or placebo with and following chemoradiotherapy, for up to 24 cycles. Chemoradiotherapy included 45 Gy external beam radiotherapy at 5 fractions per week concurrent with intravenous cisplatin (40 mg/m2) or carboplatin (area under the concentration-time curve 2) once weekly for 5 weeks, followed by image-guided brachytherapy (high-dose rate, 27·5–30 Gy or low-dose/pulse-dose rate, 35–40 Gy). Randomisation was stratified by disease stage status (FIGO stage and node status) and geographical region. Chemoradiotherapy quality was continuously reviewed. The primary endpoint was progression-free survival, assessed by the investigator using Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03830866. Findings: Between Feb 15, 2019, and Dec 10, 2020, 770 women were randomly assigned (385 to durvalumab and 385 to placebo; median age 49 years [IQR 41–57]). Median follow-up was 18·5 months (IQR 13·2–21·5) in the durvalumab group and 18·4 months (13·2–23·7) in the placebo group. At data cutoff, median progression-free survival had not been reached (95% CI not reached–not reached) for either group (HR 0·84; 95% CI 0·65–1·08; p=0·17); 12-month progression-free survival was 76·0% (71·3–80·0) with durvalumab and 73·3% (68·4–77·5) with placebo. The most frequently reported grade 3–4 adverse events in both groups were anaemia (76 [20%] of 385 in the durvalumab group vs 56 [15%] of 384 in the placebo group) and decreased white blood cells (39 [10%] vs 49 [13%]). Serious adverse events occurred for 106 (28%) patients who received durvalumab and 89 (23%) patients who received placebo. There were five treatment-related deaths in the durvalumab group (one case each of urinary tract infection, blood loss anaemia, and pulmonary embolism related to chemoradiotherapy only; one case of endocrine disorder related to durvalumab only; and one case of sepsis related to both durvalumab and chemoradiotherapy). There was one treatment-related death in the placebo group (pneumonia related to chemoradiotherapy). Interpretation: Durvalumab concurrent with chemoradiotherapy was well tolerated in participants with locally advanced cervical cancer, however it did not significantly improve progression-free survival in a biomarker unselected, all-comers population. Concurrent durvalumab plus chemoradiotherapy warrants further exploration in patients with high tumoral PD-L1 expression. Rigorous monitoring ensured high chemoradiotherapy compliance with advanced technology and allowed patients to receive optimal care. Funding: AstraZeneca.

Objective: this prospective cohort study aimed to assess the safety and efficacy of bevacizumab combined with chemotherapy in Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer. Methods: in this study, 40 Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer selected to receive bevacizumab with chemotherapy were enrolled. Patients in poor general condition were excluded. Each patient was monitored prospectively for adverse events, administration status, disease status and survival. Treatment was continued until intolerable adverse events or disease progression. The primary endpoint was safety. Results: bevacizumab plus platinum-based chemotherapy was performed for 30 patients (median cycle; 16.5), while bevacizumab plus non-platinum chemotherapy was performed for 10 patients (median cycle; 5.5). Among bevacizumab-related adverse events, hypertension occurred in 80% of patients, proteinuria in 83%, mucositis in 25%, bleeding in 20%, thromboembolic events in 5.0% and fistula in 2.5%. Gastrointestinal perforation or other life-threatening lethal adverse events were not observed. Response rate and median progression-free survival were 73% and 19.3 months for patients with bevacizumab plus platinum-based chemotherapy, and 30% and 3.9 months for patients with bevacizumab plus non-platinum chemotherapy, respectively. There was no correlation between response rate and occurrence of adverse events such as hypertension or proteinuria. Conclusion: bevacizumab combined with chemotherapy was tolerable and effective for Japanese patients with relapsed ovarian cancer, fallopian tube cancer or primary peritoneal cancer. Hypertension and proteinuria are frequently occurred and managed properly for continuing treatment.

The role of sialic acids on MUC1 in peritoneal dissemination of ovarian cancer cells was investigated. A human ovarian carcinoma cell line, ES-2, was transfected with full-length MUC1 containing 22 or 42 tandem repeats. These transfectants were less adherent to monolayers of patient-derived mesothelial cells than ES-2/mock transfectants. When these cells were inoculated into the abdominal cavity of female nude mice, mice that had received the transfectants showed better survival. When the transfectants were mixed with sialidase and injected, the survival was poorer, whereas when they were mixed with N-acetyl-2,3-dehydro-2-deoxyneuraminic acid, a sialidase inhibitor, the survival was significantly prolonged. These behaviors, concerned with peritoneal implantation and dissemination observed in vitro and in vivo, were dependent on the expression of MUC1. Therefore, sialic acid linked to MUC1 in the form, at least in part, of sialyl-T, as shown to be recognized by monoclonal antibody MY.1E12, is responsible for the suppression of adhesion of these cells to mesothelial cells and the suppression of peritoneal implantation and dissemination.

Background: Advanced relapsed ovarian cancer has a poor prognosis, and treatment options are limited. Methods: This phase I trial investigated the dosage, safety, pharmacokinetics and efficacy of trabectedin plus pegylated liposomal doxorubicin (PLD) in Japanese patients with advanced relapsed ovarian, fallopian tube, or primary peritoneal cancer. Patients received trabectedin 0.9 or 1.1 mg/m2 immediately after PLD 30 mg/m2; both drugs were given by intravenous infusion. Treatment was repeated every 21 days until disease progression or unacceptable toxicity. The maximum tolerated dose (MTD) was determined in an initial dose escalation phase, and this was used in a subsequent safety assessment phase. Safety and tumor response were monitored throughout the trial, and drug concentrations for pharmacokinetic analysis were measured during cycle 1. Results: Eighteen patients were included. The MTD of trabectedin was determined as 1.1 mg/m2. Gastrointestinal adverse events were experienced by all patients, but were mostly grade 1 or 2 in intensity. Most patients had grade ≥ 3 elevations in transaminase levels or grade ≥ 3 reductions in neutrophil count, but these events were generally manageable through dose reduction and/or supportive therapies, as appropriate. There were no deaths during the trial. Trabectedin exposure increased in a dose-dependent manner. The overall response rate was 27.8%. Conclusions: Trabectedin, in combination with PLD, may have clinical benefits in Japanese patients with relapsed advanced ovarian cancer. The recommended dosage of trabectedin for further study in this population is 1.1 mg/m2 once every 21 days. Clinical trial registration number: JapicCTI-163164

Objective: To clarify the role of radiotherapy for endometrial cancer. Methods: Data were analyzed for 39 247 patients with endometrial cancer registered with the Gynecologic Cancer Registry of the Japan Society of Obstetrics and Gynecology from 2004 to 2011. Results: The rates of 5-year overall survival (5y-OS) in the radiotherapy and surgery groups were 53.6% and 94.5% in stage I or II, and 15.5% and 67.5% in stage III or IV, respectively. The prognosis in the radiotherapy group was significantly poorer than that in the surgery group. In multivariate analysis, age, advanced stage, histological type, risk of recurrence, and initial radiotherapy were independent prognostic factors. The rates of 5y-OS with no adjuvant therapy, adjuvant chemotherapy, and adjuvant radiotherapy were 95.3%, 92.9%, and 87.1% for stage I or II, respectively, with significant differences among all groups (P < 0.001), and 60.0%, 70.4%, and 55.5% for stage III or IV, respectively, with significant differences of adjuvant chemotherapy with no adjuvant therapy (P < 0.001) and with adjuvant radiotherapy (P < 0.001). In multivariate analysis, age, advanced stage, histological type, lymphadenectomy, and adjuvant radiotherapy were independent prognostic factors. Conclusion: Patients treated with radiotherapy had a significantly poorer prognosis and the appropriate indication of radiotherapy for endometrial cancer requires further study.

Human papillomavirus (HPV) is a sexually transmitted virus with an approximately 8-kilo base DNA genome, which establishes long-term persistent infection in anogenital tissues. High levels of genetic variations, including viral genotypes and intra-type variants, have been described for HPV genomes, together with geographical differences in the distribution of genotypes and variants. Here, by employing a maximum likelihood method, we performed phylogenetic analyses of the complete genome sequences of HPV16, HPV18 and HPV58 available from GenBank (n = 627, 146 and 157, respectively). We found several characteristic clusters that exclusively contain HPV genomes from Japan: two for HPV16 (sublineages A4 and A5), one for HPV18 (sublineage A1) and two for HPV58 (sublineages A1 and A2). Bayesian phylogenetic analyses of concatenated viral gene sequences showed that divergence of the most recent common ancestor of these Japan-specific clades was estimated to have occurred ~98,000 years before present (YBP) for HPV16 A4, ~39,000 YBP for HPV16 A5, ~38,000 YBP for HPV18 A1, ~26,000 for HPV58 A1 and ~25,000 YBP for HPV58 A2. This estimated timeframe for the divergence of the Japan-specific clades suggests that the introduction of these HPV variants into the Japanese archipelago dates back to at least ~25,000 YBP and provides a scenario of virus co-migration with ancestral Japanese populations from continental Asia during the Upper Paleolithic period.

Purpose: TAS-117 is a highly potent and selective, oral, allosteric pan-AKT inhibitor under development for advanced/metastatic solid tumors. The safety, clinical pharmacology, pharmacogenomics and efficacy were investigated. Methods: This phase I, open-label, non-randomized, dose-escalating, first-in-human study enrolled patients with advanced/metastatic solid tumors and comprised three phases (dose escalation phase [DEP], regimen modification phase [RMP], and safety assessment phase [SAP]). The SAP dose and regimen were determined in the DEP and RMP. Once-daily and intermittent dosing (4 days on/3 days off, 21-day cycles) were investigated. The primary endpoints were dose-limiting toxicities (DLTs) in Cycle 1 of the DEP and RMP and incidences of adverse events (AEs) and adverse drug reactions (ADRs) in the SAP. Secondary endpoints included pharmacokinetics, pharmacodynamics, pharmacogenomics, and antitumor activity. Results: Of 66 enrolled patients, 65 received TAS-117 (DEP, n = 12; RMP, n = 10; SAP, n = 43). No DLTs were reported with 24-mg/day intermittent dosing, which was selected as a recommended dose in SAP. In the SAP, 98.5% of patients experienced both AEs and ADRs (grade ≥ 3, 67.7% and 60.0%, respectively). In the dose range tested (8 to 32 mg/day), TAS-117 pharmacokinetics were dose proportional, and pharmacodynamic analysis showed a reduction of phosphorylated PRAS40, a direct substrate of AKT. Four patients in the SAP had confirmed partial response. Conclusion: Oral doses of TAS-117 once daily up to 16 mg/day and intermittent dosing of 24 mg/day were well tolerated. TAS-117 pharmacokinetics were dose proportional at the doses evaluated. Antitumor activity may occur through AKT inhibition. Trial registration: jRCT2080222728 (January 29, 2015).

Objective: Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery. Methods: We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks). Results: Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (p =.014) was higher and a history of preterm delivery (p =.0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group (p =.0099 and.0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26–13.68, p =.019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88–46.42, p <.0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55–34.86, p =.012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24–20.73, p =.024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11–16.62, p =.035) increased the risk of preterm delivery in the multiple regression models in primiparous women. Conclusion: Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGES Prior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization. The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

The development of new treatments for gynecological malignancies has been conducted mainly through collaborative international phase III trials led by the United States and Europe. The survival outcomes of many gynecological malignancies have greatly improved as a result. Recent large-scale genome-wide association studies have revealed that drug efficacy and adverse event profiles are not always uniform. Thus, it is important to validate new treatment options in each country to safely and efficiently provide newly developed treatment options to patients with gynecological malignancies. The Japanese Gynecologic Oncology Group (JGOG) is conducting 5 cohort studies (JGOG 3026, 3027, 3028, 3030, and 3031) to establish real-world data (RWD) of poly(ADP-ribose) polymerase (PARP) inhibitor use in patients with advanced or recurrent epithelial ovarian cancer. The RWD constructed will be used to provide newly developed PARP inhibitors for women with advanced or recurrent ovarian cancer in a safer and more efficient manner as well as to develop further treatment options. In 2022, The JGOG, Korean Gynecologic Oncology Group, Chinese Gynecologic Cancer Society, and Taiwanese Gynecologic Oncology Group established the East Asian Gynecologic Oncology Trial Group to collaborate with East Asian countries in clinical research on gynecologic malignancies and disseminate new knowledge on gynecologic malignancies from Asia. The JGOG will conduct a collaborative integrated analysis of the RWD generated from Asian countries and disseminate real-world clinical knowledge regarding new treatment options that have been clinically implemented.

© Springer Nature Singapore Pte Ltd 2018. Ovarian cancer has high morbidity and mortality worldwide, and its mortality is the highest among female genital cancers. Improvement in clinical outcome is an urgent issue for ovarian cancer, and clinical management including treatment has been repeatedly studied. Tumor markers such as CA125, CA19-9, and HE4 and image diagnosis using MRI, CT, PET, etc. are indispensable diagnostic aid tools. In the initial treatment, primary debulking surgery (PDS) is basically effective, but fertility preservation can be considered depending on the case. For advanced cancers, interval debulking surgery (IDS) is considered after several cycles of neoadjuvant chemotherapy (NAC). Although the combination of paclitaxel and carboplatin (TC) regimen was originally established as the standard chemotherapy for ovarian cancer regardless of tissue type, new treatments in clinical trials, including molecular-targeted therapeutic agents, are being investigated. The main treatment for recurrent cancer is chemotherapy, and sensitivity to chemotherapy based on the disease-free interval has been considered in the choice of treatment. Furthermore, in recent years, risk-reducing bilateral salpingo-oophorectomy has been undertaken to prevent the onset of hereditary breast and ovarian cancer. It is also being studied how to manage the follow-up after treatment and hormone replacement.

The AT-rich interacting domaincontaining protein 1A gene (ARID1A) encodes ARID1A, a member of the SWI/SNF chromatin remodeling complex. Mutation of ARID1A induces changes in expression of multiple genes (CDKN1A, SMAD3, MLH1 and PIK3IP1) via chromatin remodeling dysfunction, contributes to carcinogenesis, and has been shown to cause transformation of cells in association with the PI3K/AKT pathway. Information on ARID1A has emerged from comprehensive genomewide analyses with nextgeneration sequencers. ARID1A mutations have been found in various types of cancer and occur at high frequency in endometriosisassociated ovarian cancer, including clear cell adenocarcinoma and endometrioid adenocarcinoma, and also occur at endometrial cancer especially in endometrioid adenocarcinoma. It has also been suggested that ARID1A mutation occurs at the early stage of canceration from endometriosis to endometriosisassociated carcinoma in ovarian cancer and also from atypical endometrial hyperplasia to endometrioid adenocarcinoma in endometrial cancer. Therefore, development of a screening method that can detect mutations of ARID1A and activation of the PI3K/AKT pathway might enable early diagnosis of endometriosisassociated ovarian cancers and endometrial cancers. Important results may also emerge from a current clinical trial examining a multidrug regimen of temsirolimus, a small molecule inhibitor of the PI3K/AKT pathway, for treatment of advanced ovarian clear cell adenocarcinoma with ARID1A mutation and PI3K/AKT pathway activation. Also administration of sorafenib, a multikinase inhibitor, can inhibit cancer proliferation with PIK3CA mutation and resistance to mTOR inhibitors and GSK126, a moleculartargeted drug can inhibit proliferation of ARID1Amutated ovarian clear cell adenocarcinoma cells by targeting and inhibiting EZH2. Further studies are needed to determine the mechanism of chromatin remodeling dysregulation initiated by ARID1A mutation, to develop methods for early diagnosis, to investigate new cancer therapy targeting ARID1A, and to examine the involvement of ARID1A mutations in development, survival and progression of cancer cells.

PURPOSE: Clear cell carcinoma (CCC) is a rare histologic subtype that demonstrates poor outcomes in epithelial ovarian cancer. The Japanese Gynecologic Oncology Group conducted the first randomized phase III, CCC-specific clinical trial that compared irinotecan and cisplatin (CPT-P) with paclitaxel plus carboplatin (TC) in patients with CCC. PATIENTS AND METHODS: Six hundred sixty-seven patients with stage I to IV CCC of the ovary were randomly assigned to receive irinotecan 60 mg/m(2) on days 1, 8, and 15 plus cisplatin 60 mg/m(2) on day 1 (CPT-P group) every 4 weeks for six cycles or paclitaxel 175 mg/m(2) plus carboplatin area under the curve 6.0 mg/mL/min on day 1 every 3 weeks for six cycles (TC group). The primary end point was progression-free survival. Secondary end points were overall survival, overall response rate, and adverse events. RESULTS: Six hundred nineteen patients were clinically and pathologically eligible for evaluation. With a median follow-up of 44.3 months, 2-year progression-free survival rates were 73.0% in the CPT-P group and 77.6% in TC group (hazard ratio, 1.17; 95% CI, 0.87 to 1.58; P = .85). Two-year overall survival rates were 85.5% with CPT-P and 87.4% with TC (hazard ratio, 1.13; 95% CI, 0.80 to 1.61; one-sided P = .76). Grade 3/4 anorexia, diarrhea, nausea, vomiting, and febrile neutropenia occurred more frequently with CPT-P, whereas grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy, and joint pain occurred more frequently with TC. CONCLUSION: No significant survival benefit was found for CPT-P. Both regimens were well tolerated, but the toxicity profiles differed significantly. Treatment with existing anticancer agents has limitations to improving the prognosis of CCC.

OBJECTIVE: To investigate pregnancy outcomes in women after abdominal radical trachelectomy (RT) for early-stage cervical cancer. METHODS: The patients' background, fertility, and pregnancy outcomes were reviewed in a total of 61 pregnancies in 48 of 172 women who underwent abdominal RT at Keio University Hospital between September 2002 and December 2013. RESULTS: There were 5 women with stage IA1, 2 with stage IA2, and 41 with stage IB1. Histological types were as follows: squamous cell carcinoma (n = 36), adenocarcinoma (n = 10), and adenosquamous cell carcinoma (n = 2). The pregnancy rate of women attempting to conceive after abdominal RT was 44% (48/109). The mean +/- SD duration from abdominal RT to conception was 3.1 +/- 1.9 years. Of 61 pregnancies, 42 pregnancies were achieved by fertility treatment (in vitro fertilization-embryo transfer, 39; intrauterine insemination, 3). After excluding one pregnancy without detailed clinical information, there were 42 live births (5 in 22-27 weeks, 11 in 28-33weeks, 20 in 34-36 weeks, and 6 in 37-38 weeks), 13 miscarriages, and 5 ongoing pregnancies. While there were 10 first trimester miscarriages, 3 pregnancies ended in the second trimester owing to chorioamnionitis. The mean gestational age at birth was 33 weeks of pregnancy. Thirty-seven neonates were appropriate-for-date, and one was small-for-date. Six pregnancies exhibited massive bleeding from the residual cervix in the late pregnancy. Preterm birth less than 34 weeks of pregnancy was related to premature rupture of the membrane (P < 0.05). Chorioamnionitis was evident in 9 of 11 pregnancies with preterm premature rupture of the membrane followed by birth at less than 34 weeks of pregnancy. No parturients exhibited lochiometra and endometritis postpartum. CONCLUSIONS: Abdominal RT provided favorable pregnancy outcomes, and fertility treatment could be advantageous to conception. Massive bleeding from the residual cervix as well as ascending infection might be characteristic features during pregnancy after abdominal RT.