Hypofractionated radiation leads to more rapid bleeding cessation in women with vaginal bleeding secondary to gynecologic malignancy.

BACKGROUND: Vaginal bleeding (VB) is common in women with gynecologic (GYN) malignancies. Radiation therapy (RT) is used for the definitive treatment of GYN cancers and palliation of bleeding. The historical dogma is that high dose-per-fraction radiation leads to more rapid bleeding cessation, yet there is scant data supporting this claim. We sought to examine the effect of RT fraction size on VB via retrospective analysis of patients receiving hypofractionated radiation (HFRT) compared to conventionally fractionated radiation (CFRT) for control of bleeding secondary to GYN malignancies. METHODS: We identified patients receiving external beam RT for continuous VB from GYN malignancy treated in our department from 2012 to 2020. RT was classified as HFRT (> 2.0 Gy/fx) or CFRT (1.8-2.0 Gy/fx). Demographic information, disease characteristics, and treatment details were collected. The primary endpoint was days from RT initiation until bleeding resolution. Characteristics between groups were compared via Fisher's exact test. Time to bleeding cessation was assessed via Kaplan-Meier and log-rank test. Univariable and multivariable Cox-proportional hazards were used to identify factors associated with bleeding cessation. RESULTS: We identified 43 patients meeting inclusion criteria with 26 and 17 patients receiving CFRT and HFRT, respectively. Comparison of baseline characteristics revealed patients receiving HFRT were older (p = 0.001), more likely to be post-menopausal (p = 0.002), and less likely to receive concurrent chemotherapy (p = 0.004). Time to bleeding cessation was significantly shorter for patients receiving HFRT (log-rank p < 0.001) with median time to bleeding cessation of 5 days (HFRT) versus 16 days (CFRT). Stratification by dose-per-fraction revealed a dose-response effect with more rapid bleeding cessation with increased dose-per-fraction. While HFRT, age, recurrent disease, prior pelvic RT, and prior systemic therapy were associated with time to bleeding cessation on univariable analysis, HFRT was the only factor significantly associated with time to bleeding cessation in the final multivariable model (HR 3.26, p = 0.008). CONCLUSIONS: Patients with continuous VB from GYN tumors receiving HFRT experienced more rapid bleeding cessation than those receiving CFRT. For patients with severe VB, initiation of HFRT to control malignancy related bleeding quickly may be warranted.

Metastatic renal cell carcinoma initially presenting with hematochezia and subsequently with vaginal bleeding: a case report.

BACKGROUND: We report an unusual case of a synchronous rectal and metachronous vaginal metastatic renal cell carcinoma. CASE PRESENTATION: A 78-year-old woman presented with hematochezia and a colonoscopy revealed a metastatic clear-cell renal cell carcinoma rectal polyp biopsy-proven. Abdominal computed tomography identified a 9.0-cm left renal mass with renal vein thrombosis, for which she underwent a laparoscopic radical nephrectomy. Histopathological examination confirmed a pT3a clear-cell renal cell carcinoma. Seven months later, the patient presented with vaginal bleeding. Physical examination revealed a vaginal polypoid mass and biopsy confirmed a clear-cell renal cell carcinoma metastasis. CONCLUSIONS: This case represents unusual manifestations of metastatic renal cell carcinoma and is a reminder of the wide spectrum of clinical course of this disease.

[Current indications for uterine artery embolization to treat postpartum hemorrhage]. / Place actuelle de l'embolisation artérielle dans la prise en charge des hémorragies graves du post-partum immédiat.

Uterine artery embolization is an interventional radiology technique successfully used for more than 30 years in the management of gynecological or obstetrical hemorrhage. Precise indications for uterine artery embolization to treat postpartum hemorrhage have been recently published. Uterine artery embolization is indicated in case of uterine atony despite medical treatment particularly after vaginal delivery, in case of vaginal thrombus or cervical tear after failed surgical repair. Embolization can also be discussed in case of persistent hemorrhage after arterial ligation or hysterectomy. Finally, arterial embolization can be attempted in case of placenta accreta to avoid hysterectomy. In all situations, pluridisciplinary management of patients with involvement of interventional radiologists, anesthesiologists and obstetricians is mandatory. Early transportation of patients for embolization should be discussed taking into consideration time of onset of hemorrhage, expected transfer time and treatment options available on site. For validated indications, success rates of arterial embolization as high as 80% can be expected in experienced hands.

Palliative radiation therapy for gynaecological malignancies.

Patients with advanced, recurrent, or metastatic gynaecological malignancies constitute a heterogenous population with diverse symptomatology. Progressive abdominopelvic disease can result in vaginal or diffuse pelvic bleeding, pain, and visceral or lymphovascular obstruction. Gynaecological cancer can also develop debilitating metastases, in particular to bone, central nervous system, or chest. Radiation therapy is a local-regional treatment modality, that, when applied judiciously, can lead to substantial symptomatic relief and tumour response. Individualized application is necessary, balancing efficacy and patient convenience versus treatment intensity, expected duration of palliation and potential toxicity. Important factors to consider are a patient's performance status, extent and sites of tumour, specific symptoms, and life expectancy. The optimal incorporation of radiotherapy is best achieved in the context of a multidisciplinary approach that addresses all facets of palliative care in patients with incurable gynaecological malignancies, to maximize their quality of life and functional level.

Intracavitary radiotherapy for refractory dysfunctional uterine bleeding. A case report.

BACKGROUND: Pelvic irradiation was once a common treatment for dysfunctional uterine bleeding (DUB). Today the majority of women with DUB are successfully treated with hormonal therapy; patients unresponsive to hormonal therapy may require endometrial ablation or hysterectomy. We present a patient with severe, intractable DUB and contraindications to surgery who was treated with intracavitary radiotherapy. CASE: A 39-year-old, 150-cm-tall, 310-kg woman was referred for management of severe DUB refractory to medical management. The bleeding was successfully treated with intracavitary cesium. Hysterectomy was not recommended due to the operative risks posed by the patient's massive obesity. Because of technical difficulties during a previous dilation and curettage and the expense of long-term GnRH agonist therapy, the patient elected to undergo intracavitary radiotherapy. CONCLUSION: In selected patients, intracavitary radiotherapy can be used to treat DUB when conventional therapy fails or is contraindicated.

Two case reports: carcinoma of the cervix and carcinoma of the endometrium treated with radiotherapy after previous irradiation for benign uterine bleeding.

In the 1940s, 1950s and 1960s, low doses of radiotherapy were used to treat benign uterine bleeding. The cases of two women who received this form of therapy and later developed gynaecological malignancies and had high-dose pelvic radiotherapy are presented. A 76-year-old woman with an International Federation of Gynecology and Obstetrics (FIGO) stage-IIB squamous cell carcinoma of the cervix received external beam radiotherapy and intra-uterine brachytherapy and a 77-year-old women with a FIGO stage-IB endometrial adenocarcinoma received adjuvant postoperative pelvic radiotherapy. Both women had a significant past history of low-dose-rate intra-uterine irradiation for dysfunctional uterine bleeding. Therefore the theoretical question of carcinogenesis was raised, and also the practical questions of what dose had previously been given and what further dose could be safely given with regard to normal tissue tolerance.

Hemostatic radiotherapy in carcinoma of the uterine cervix.

OBJECTIVE: To evaluate the treatment of hemorrhagic carcinoma of the uterine cervix with hemostatic radiotherapy (external and intracavitary radiotherapy). METHOD: Twenty cases of refractory hemorrhagic carcinoma of the uterine cervix receiving hemostatic radiotherapy between April 1987 and May 1992 were analyzed. The age of the patients ranged between 30 and 60 years with a median of 42 years. RESULTS: The mean tumor volume was 130 mm3; all cases were classified as FIGO stage IIb (n = 8), IIIb (n = 11) or IVa (n = 1). Radiotherapy was carried out either by the external or intracavitary technique. The control of hemorrhage was 100% within 12-48 h after radiotherapy. However 85% of patients failed locally in the form of residual, recurrent pelvic or metastatic disease, within 24 months of follow-up. CONCLUSION: Hemorrhagic cervical cancer has a poor prognosis.

A case report on radiotherapy in choriocarcinoma: a life saving procedure.

Radiation therapy was tried to control hemorrhage from uterine cavity in a case of choriocarcinoma in which surgery was not practically possible due to the presence of a large nodule extending from suburethral region up to anterior fornix involving the entire anterior vaginal wall and patient being in a very critical condition. Radiotherapy was found to be successful and life saving.

Mortality in a cohort of women given X-ray therapy for metropathia haemorrhagica.

Mortality to January 1, 1991, has been studied in 2,067 women in Scotland given X-ray therapy for metropathia haemorrhagica during the period 1940-1960. Average follow-up was 28 years. Overall, 1,313 deaths were observed compared with 1,297.01 expected from Scottish rates [standardized mortality ratio (SMR): 1.01]. Mortality was increased for cancers of heavily irradiated pelvic sites (SMR 5+ years after irradiation: 1.46) following mean doses to organs in the vicinity of the pelvis in the range 2.6-5.3 Gy. For these cancers the SMR was higher 30+ years after irradiation than at 5-29 years, indicating that the effects of exposure last for over 30 years, and in this period bladder cancer mortality was exceptionally high (SMR = 4.91). Mortality was also raised for leukaemia (SMR 2+ years after irradiation: 2.05), following a mean bone-marrow dose of 1.3 Gy, and for multiple myeloma (SMR 5+ years after irradiation: 2.59). For leukaemia the SMR was lower 30+ years after irradiation than at earlier periods, but remained greater than unity. For other cancers mortality was similar to Scottish rates, except for breast cancer for which mortality was low (SMR 5+ years after irradiation: 0.53), even in women aged over 50 at irradiation (SMR 5+ years after irradiation: 0.14). The deficit was principally due to a large deficit of breast cancer in women with ovarian doses of at least 5 Gy.

Cancer mortality following radium treatment for uterine bleeding.

Cancer mortality in relation to radiation dose was evaluated among 4153 women treated with intrauterine radium (226Ra) capsules for benign gynecologic bleeding disorders between 1925 and 1965. Average follow up was 26.5 years (maximum = 59.9 years). Overall, 2763 deaths were observed versus 2687 expected based on U.S. mortality rates [standardized mortality ratio (SMR) = 1.03]. Deaths due to cancer, however, were increased (SMR = 1.30), especially cancers of organs close to the radiation source. For organs receiving greater than 5 Gy, excess mortality of 100 to 110% was noted for cancers of the uterus and bladder 10 or more years following irradiation, while a deficit was seen for cancer of the cervix, one of the few malignancies not previously shown to be caused by ionizing radiation. Part of the excess of uterine cancer, however, may have been due to the underlying gynecologic disorders being treated. Among cancers of organs receiving average or local doses of 1 to 4 Gy, excesses of 30 to 100% were found for leukemia and cancers of the colon and genital organs other than uterus; no excess was seen for rectal or bone cancer. Among organs typically receiving 0.1 to 0.3 Gy, a deficit was recorded for cancers of the liver, gall bladder, and bile ducts combined, death due to stomach cancer occurred at close to the expected rate, a 30% excess was noted for kidney cancer (based on eight deaths), and there was a 60% excess of pancreatic cancer among 10-year survivors, but little evidence of dose-response. Estimates of the excess relative risk per Gray were 0.006 for uterus, 0.4 for other genital organs, 0.5 for colon, 0.2 for bladder, and 1.9 for leukemia. Contrary to findings for other populations treated by pelvic irradiation, a deficit of breast cancer was not observed (SMR = 1.0). Dose to the ovaries (median, 2.3 Gy) may have been insufficient to protect against breast cancer. For organs receiving greater than 1 Gy, cancer mortality remained elevated for more than 30 years, supporting the notion that radiation damage persists for many years after exposure.

Leukemia following radiotherapy for uterine bleeding.

Mortality due to leukemia among 4483 women treated with radiation to control uterine bleeding between 1925 and 1965 was twice as high as expected based on U.S. population rates (standardized mortality ratio (SMR) = 2.0; 95% confidence interval (CI): 1.4 to 2.8). Women were followed for an average of 26.4 years. Relative risk was highest 2 to 5 years after treatment (SMR = 8.1) and among women over 55 years at irradiation (SMR = 5.8). The usual method of treatment was intrauterine radium. Average radiation dose to active bone marrow was estimated on the basis of original radiotherapy records (median, 53 cGy). A linear dose-response model provided an adequate fit to the data. The average excess relative risk was 1.9% per cGy (95% CI: 0.8 to 3.2), and the average absolute risk was 2.6 excess leukemia deaths per million women per year per cGy (95% CI: 0.9 to 4.8). Chronic myeloid leukemia predominated during the first 15 years following exposure, whereas acute leukemias and chronic lymphatic leukemia were most common thereafter. The radiation doses experienced during treatment of benign gynecologic disease appear to result in greater leukemia risk per cGy average marrow dose than the considerably higher doses used to treat malignant disease, perhaps because of a decreased likelihood of killing potentially leukemic cells.

Cardiovascular death after radiotherapy for benign bleeding disorders. The Radiumhemmet metropathia cohort 1912-1977.

Of 788 women treated with ionizing irradiation for benign bleeding disorders (metropathia) 308 (39%) died of cardiovascular disease. In a control group, consisting of 1219 women with metropathia who were not irradiated, 257 (21%) cardiovascular deaths occurred. Although the risk of cardiovascular death in the two studied cohorts compared with national death rates was only 0.92 (lower limit 0.82; upper limit 1.03) and 0.88 (lower limit 0.78; upper limit 0.99) respectively, it was found that women irradiated before the menopause (age 50 years) run a higher risk of cardiovascular death than the controls in the same age group and those irradiated after the menopause.

Radiotherapy in benign uterine bleeding disorders. The Radiumhemmet metropathia cohort 1912-1977. Short and long term results.

Radiotherapy was earlier a method of choice for treatment of benign bleeding disorders (metropathia), especially in women of high surgical risk. During the period 1912 to 1977 933 women with benign bleeding disorders were treated at Radiumhemmet with intracavitary brachytherapy or external irradiation or a combination of both. The result with regard to cure of the uterine bleedings was good (48%). Hormonal withdrawal symptoms after treatment were noted in 45% of the patients. In the long term follow up an increased risk of cardiovascular death was found in women treated before menopause. Malignant tumours occurred in 107 cases versus 90.2 expected (RR 1.19). The estimated ovarian dose of ionizing radiation varied from 3.5 Gy to 6.0 Gy for the three standard techniques. Two women gave birth to a healthy child 4 and 5 years after intracavitary radium treatment. The estimated absorbed dose to the ovaries in these two women were 1 Gy and 4 Gy, respectively.

Effect of low dose endometrial after-loading irradiation upon the hypophysis-ovarian axis.

Endometrial inactivation by irradiation, while simultaneously preserving the ovarian function is sometimes clinically indicated. We have found that after 1100 cGy (rad) the ovarian function remains intact, yet endometrial inactivation is unsatisfactory. Therefore, four premenopausal subjects, with clinical indications for eliminating disturbing uterine bleedings, received each an endometrial dose of 1600 cGy by using a Cathetron afterloading unit. When pre- and post-treatment cycles were compared, the circulating gonadotrophin and estrogen levels were unchanged in three subjects. Nine to 12 weeks after the treatments there were no signs of ovulation and the gonadotrophin levels were generally increased. None of the subjects had experienced any bleedings. We conclude that an endometrial dose of 1600 cGy is effective in inactivating endometrium, but may also lead to an impaired ovarian function and to a premature menopause.

[Intracavitary radiotherapy of benign recurrent uterine bleedings (author's transl)]. / Intrakavitäre Kontaktbestrahlung bei rezidivierenden Blutungen gutartiger Histogenese.

387 patients with uterine bleeding resistant to other therapy were treated by intracavitary radium-therapy. In all cases there was a contraindication for the operative removal of the uterus. In 94,3% of our cases the bleeding could be treated successfully by the radium-application. Side effects of the irradiation occurred only in a minimal and neglectable percentage. Therefore the intrauterine contact-irradiation-therapy should be remembered in cases of uterine bleeding resistant to hormonal therapy or in cases of high risk for operation. With the new and modern afterloading device the molestation for the patients could be reduced to a minimum.

The influence of radiation on fertility in man.

Increasing numbers of young people are now being cured of certain neoplasms by radiotherapy and chemotherapy. Such people will naturally wish to lead a normal life and possibly to have children. Therefore the question of the effect of radiation and cytotoxic drugs on the reproductive capacity of these patients has become important. The purpose of this report is to review the information available on the effect of radiation on fertility in man. Direct information on radiation effects on human fertility is available from reports on therapeutic exposure and deliberate experimental exposure. Although the total number of cases involved is small, a number of general principles emerge. In males, fractionated irradiation of the testes may be more harmful than acute, at least up to total doses of about 600 cGy (rad). Fractionated doses greater than 35 cGy cause aspermia, the time taken for recovery increasing with dose, and after more than 200 cGy aspermia may be permanent. In females, response varies with age as well as dose. For example, 400 cGy may cause a 30% incidence of sterility in young women, but in women aged above 40 years it results in 100% sterility. However, individuals of either sex show a degree of variation in their response to irradiation.

Late effects of x irradiation in patients treated for metropathia haemorrhagica.

We have previously reported on the causes of death among 2,068 patients treated with X irradiation for metropathia haemorrhagica at three Scottish radiotherapy centres between 1940 and 1960 (Doll and Smith, 1968). This cohort of women has now been followed up for a further seven years. 500 (24 per cent) women have now died, 78 (3-8 per cent) have emigrated and 25 (1-2 per cent) could not be traced. The numbers of deaths from different causes have been compared with the numbers expected in a population of similar age and sex exposed to the Scottish national mortality rates over the same period. An excess of deaths from leukaemia (seven observed, 2-3 expected) and of cancers of the heavily irradiated sites (59 observed, 40-1 expected) continues to be observed five or more years after treatment. There is no indication of any change in the excess death rate, due to cancers of sites in the radiation field, with time since treatment up to at least 20 years after the radiation exposure. Over the same period the number of deaths from cancer of the breast was below expectation (ten observed, 22-3 expected) and no increased mortality from coronary disease was seen (102 observed, 100-9 expected). The mean dose of radiation to the bone marrow has been determined for each woman ant it is estimated that the excess rate of leukaemia in the first 20 years after treatment is about 1-1 per million women per year per rad. This figure is in accord with the estimates derived from the survivors of the atomic bomb explosions in Hiroshima and Nagasaki and among patients with ankylosing spondylitis treated with X irradiation. However, the finding of no excess risk of leukemia among women treated with irradiation for cancer of the cervix (Hutchison, 1968) suggests that the simple assumption of a linear dose-response relationship for leukaemia is incorrect, at least when high doses of radiation are delivered to a small volume of marrow.