High-dose insulin and dexamethasone combined with radiotherapy in endometrial stromal sarcoma recurring with multiple metastases: A case report.

RATIONALE: Endometrial stromal sarcoma (ESS) is a rare malignant tumor. There is insufficient data supporting the efficiency of current treatments in multiple metastatic settings, and novel therapeutic options for ESS are considered an area of high unmet clinical need. PATIENT CONCERNS: We report the case of a 28-year-old woman who was diagnosed with ESS after undergoing total hysterectomy and left adnexectomy at another hospital. Two years later, the disease recurred, with multiple abdominal cavities and lung metastases. The patient was treated with a variety of chemotherapeutic drugs, including tyrosine kinase inhibitors, at the same hospital; however, none of them inhibited disease progression. DIAGNOSES: Computed tomography (CT) revealed multiple masses in the abdominal and pelvic cavities and multiple pulmonary nodules. Ultrasound-guided biopsy was performed and the tumor tissue was histologically confirmed after treatment. INTERVENTIONS: Insulin 300-400 IU was administrated by intravenous infusion in 10% glucose (500 mL) with disodium adenosine triphosphate 60 mg, coenzyme A 100 units, 10% potassium chloride 5 mL and 25% magnesium sulfate 5 mL. Dexamethasone (20-25 mg/d) was diluted with 10 mL of 2% lidocaine and then intraperitoneally injected after ascites draw. After 9 months, the patient was referred to another center for radiotherapy. OUTCOMES: CT images tomography showed recurrent pelvic masses, and multiple abdominal cavity and lung metastases gradually shrunk with treatment. Histological biopsy revealed growth arrest of tumor cells. The patient experienced for 3-years survival. LESSONS: High-dose insulin and dexamethasone combined with radiotherapy provides a novel and promising option for patients with multiple ESS metastases.

Volumetric-modulated arc therapy with vaginal cuff simultaneous integrated boost as an alternative to brachytherapy in adjuvant irradiation for endometrial cancer: a prospective study.

AIM: To report preliminary results of a prospective study using pelvic volumetric-modulated arc therapy and simultaneous integrated boost (SIB-VMAT) on vaginal cuff postoperatively in patients with endometrial cancer (EC). PATIENTS AND METHODS: Fifty consecutive patients, submitted surgery for EC, were recruited to SIB-VMAT prescribing a dose of 54 Gy to the pelvis and 66 Gy to the vaginal cuff in 30 fractions. A 2 mm transvaginal probe and magnetic resonance imaging were used to define the vaginal cuff. Toxicity data were collected according to Common Terminology Criteria for Adverse Events v4.0; clinical outcomes were analyzed. RESULTS: The median follow-up was 26 (range=12 to 39) months. According to International Federation of Gynecology and Obstetrics 2009, the stages were: IB1 in 20%, IB2 in 28%, IIA2 in 16%, IIB in 6%, IIIA in 2%, and IIIC in 28%. The 2-year Overall Survival and Local Control were 96% and 100%, respectively. Two pelvic node failures were registered. Acute gastrointestinal toxicity was: G0 in 12%, G1 in 52%, G2 in 36%; no case of toxicity G3 or more was observed. Acute genitourinary toxicity was: G0 in 10%, G1 in 42%, G2 in 48%; no case of toxicity G3 or more was observed. No late severe gastrointestinal or genitourinary toxicities were reported. A statistical correlation was found between acute G2 gastrointestinal toxicity with bowel V20 Gy ≥ 30%, V20 ≥ 40%, V30 ≥ 30%, Dmax ≥ 45 Gy. Acute G2 genitourinary toxicity was threefold higher with chemotherapy. CONCLUSION: In patients with EC, SIB-VMAT is feasible, and well tolerated. Preliminary data of clinical outcome are promising. Further prospective studies are advocated.

Dosimetric feasibility of stereotactic body radiation therapy as an alternative to brachytherapy for definitive treatment of medically inoperable early stage endometrial cancer.

PURPOSE: This study was designed to evaluate the dosimetric feasibility of definitive stereotactic body radiation therapy (SBRT) for the treatment of medically inoperable early stage endometrial cancer. METHODS: CT simulation scans from 10 medically inoperable early stage endometrial cancer patients previously treated with high dose-rate (HDR) intracavitary brachytherapy were used to generate Helical Tomotherapy (HT) plans using the IMRT mode with clinical target volumes (CTVs) that included the uterus plus cervix. A prescription dose of 34 Gy in 4 fractions was used. The SBRT dosimetry was compared to the 10 prior intracavitary brachytherapy plans normalized to a standard dose. Organs at risk (OARs) evaluated were the bladder, rectum, sigmoid, femoral heads, and other bowel, including both large and small bowel. The simulation CT and daily image guidance for 4 patients treated with this technique were evaluated to assess for interfraction variation in the uterine position and effects on dosimetry. RESULTS: Compared to intracavitary brachytherapy, HT SBRT produced significantly greater overall target coverage to the uterus, boost CTV, and PTV, with exception of the V150% of the uterus. HT SBRT significantly increased dose to the rectum, bowel, and femoral heads compared to intracavitary brachytherapy, though not outside of dose tolerance limits. Review of daily image guidance for patients treated with this technique demonstrated good reproducibility with a mean overlap index of 0.87 (range, 0.74 - 0.99). CONCLUSIONS: Definitive SBRT for medically inoperable early stage endometrial cancer appears to be a feasible treatment option. Future studies are warranted to evaluate long-term clinical outcomes with this technique, compared to HDR intracavitary brachytherapy.

Supporting patients following pelvic radiotherapy for endometrial cancer.

Endometrial cancer is the commonest gynaecological cancer in the UK. Affected women often live with long-term complex and debilitating side-effects of radiotherapy treatment, such as bowel toxicity, fatigue and psychosexual problems. Women also experience negative feelings around self-image and sexuality, which contribute to a decline in their quality of life. A review of the literature and national policy showed that women had unmet needs after completing radiotherapy treatment for endometrial cancers, and that cancer nurse specialists are in a prime position to deliver a holistic package of personalized care. Staff at a nurse-led gynaecology oncology clinic performed an audit that found the clinic was not meeting the longer-term needs of most women after radiotherapy for endometrial cancers, and that women were attending multiple appointments to access different services. The clinical nurse specialist reviewed local and national policy, carried out situational analysis and engaged with service users to identify where change was needed and to examine whether a new model of service provision, where patients could consult different professionals at one appointment, would help the move forward in life after treatment.

Local α-tocopherol for acute and short-term vaginal toxicity prevention in patients treated with radiotherapy for gynecologic tumors.

INTRODUCTION: Data in literature about the use of adjuvant treatment to reduce acute adverse effects of radiotherapy on the pelvis are scant, with the exception of a few reports on the topical use of estrogen, which promotes proliferation of epithelium. MATERIALS AND METHODS: In this prospective trial, α-tocopherol acetate was topically administered to patients affected by endometrial and cervical cancer and undergoing radiation treatment to avoid acute vaginal complications. RESULTS: Vaginal application of α-tocopherol reduced vaginal toxicity and pain, although vaginal secretion was not significantly different in the 2 groups studied. The histological scoring system showed a significant reduction of inflammation, no difference in fibrosis, and an increase of acanthosis. CONCLUSIONS: The use of α-tocopherol as adjuvant treatment to reduce the acute adverse effects of radiotherapy on the vagina should be considered.

Adjuvant chemotherapy in endometrial cancer.

The indications for adjuvant therapy in endometrial cancer are briefly reviewed. The importance of systemic adjuvant therapy is emphasized. A short summary of randomized studies on adjuvant chemotherapy versus radiotherapy and on adjuvant sequential chemotherapy plus radiotherapy versus radiotherapy alone is given. On the basis of the present results from randomized trials, a combination of adjuvant radiotherapy and platinum-based chemotherapy seems to be most effective.

[Current strategies in radiotherapy for cervical and endometrial carcinoma].

We used combinations of taxan-based neoadjuvant and adjuvant full-dose chemotherapy and aggressive combined radiotherapy including clinical target volume extension, increased total dosage, hyperthermia, cryo- and local chemotherapy as radiosensitizers, for treatment of invasive and locally-advanced breast cancer or endometrial carcinoma with poor prognosis. 3D-ultrasound/CT/MRI--based designing of radiotherapy and monitoring of dynamic definition of target volume and "high risk volume" in organs at risk in cases of tumor progression was an indispensable measure. As a result, no local recurrence was reported in 73% for 36 months.

The role of multi-modality adjuvant chemotherapy and radiation in women with advanced stage endometrial cancer.

OBJECTIVE: : The optimal adjuvant therapy for women with stages III and IV endometrial cancer following surgical staging and cytoreductive surgery is controversial. We sought to determine the outcome of patients with advanced stage endometrial cancer treated with postoperative chemotherapy+/-radiation to determine whether there was an advantage to combining treatment modalities. METHODS: : A retrospective analysis of patients with surgical stages III and IV endometrial cancer from 1975 to 2006 was conducted at Duke University and the University of North Carolina. Inclusion criteria were comprehensive staging procedure including hysterectomy, bilateral salpingo-oophorectomy, +/-selective pelvic/aortic lymphadenectomy, surgical debulking, and treatment with adjuvant chemotherapy and/or radiotherapy. Progression-free (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: : 356 Patients with advanced stage endometrial cancer were identified who received postoperative adjuvant therapies; 48% (n=171) radiotherapy alone, 29% (n=102) chemotherapy alone, 23% (n=83) chemotherapy and radiation. The median age was 66 years; 38% had endometrioid tumors; and 83% were optimally debulked. There was a significant difference between the adjuvant treatment groups for both OS and PFS (p<0.001), with those receiving chemotherapy alone having poorer 3-year OS (33%) and PFS (19%) compared to either radiotherapy alone (70% and 59%) or combination therapy (79% and 62%). After adjusting for stage, age, grade, and debulking status the hazard ratio (HR) for OS was 1.60 (95% CI, 0.88 to 2.89; p=0.122) for chemotherapy alone and 2.01 (95% CI, 1.17 to 3.48; p=0.012) for radiotherapy alone, compared to combination therapy. When the analysis was restricted to optimally debulked patients the adjusted HR for patients who were treated with either chemotherapy or radiation alone indicated a significantly higher risk for disease progression [HR=1.84 (95% CI, 1.03 to 3.27; p=0.038); HR=1.80 (95% CI, 1.10 to 2.95; p=0.020)] and death [HR=2.33 (95% CI, 1.12 to 4.86; p=0.024); HR=2.64 (95% CI, 1.38 to 5.07; p=0.004)], respectively, compared to patients who received combination therapy. CONCLUSION: : Combined adjuvant chemotherapy and radiation was associated with improved survival in patients with advanced stage disease compared to either modality alone. Future clinical trials are needed to prospectively evaluate multi-modality adjuvant therapy in women with advanced staged endometrial cancer to determine the appropriate sequencing and types of chemotherapy and radiation.

Twelve-year experience in the management of endometrial cancer: a change in surgical and postoperative radiation approaches.

OBJECTIVE: Over the past 12 years, the primary management of endometrial cancer at a comprehensive cancer center has undergone changes characterized by the increased use of laparoscopic surgery with comprehensive staging resulting in a decreased reliance on postoperative adjuvant whole pelvic radiation therapy (WPRT). The purpose of this study was to analyze the results of these changes. MATERIALS AND METHODS: Between 1/93 and 12/04, 1312 patients underwent surgery for endometrial cancer consisting of either abdominal or laparoscopic hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO or LAVH/BSO). Pelvic and para-aortic lymph node dissection was performed at the discretion of the attending physician. Postoperative adjuvant treatment employed in patients with high-risk features consisted mainly of WPRT+/-intravaginal radiation therapy (IVRT). Total direct medical charges incurred from 10 days prior to surgery through 75 days after surgery were determined with charges converted to direct medical costs, taking into account inflationary changes. RESULTS: The median age at diagnosis for all patients was 62 years (range, 21-93 years), with a median follow-up of 31.6 months (range, 0-140 months). There was a significant increase in LAVH/BSO versus TAH/BSO (P<0.001) until 2001 when we began participating in a national randomized trial of laparoscopic versus abdominal surgery. In addition, there was a significant increase in the percentage of patients undergoing lymph node dissection as well as the median number of nodes removed (P<0.001). This was associated with a significant decrease in the use of WPRT during 1993-1998 versus 1999-2004 (P<0.001). The use of IVRT remained the same during these time periods. There was no significant difference in 1-, 2-, or 5-year survival for patients treated in either time period. Cost data were available from 1995 to 2004. There was a significant increase in the median total direct medical costs when comparing periods 1995-1998 with 1999-2004 (P<0.001), although the median cost of pelvic radiation therapy was lower in the later time period. CONCLUSION: Over a 12-year period, the primary management of endometrial cancer changed to include an increased use of laparoscopy and comprehensive surgical staging and a decrease in the use of postoperative adjuvant WPRT, with no appreciable negative effect on overall survival.

A dosimetric analysis of intensity-modulated radiation therapy (IMRT) as an alternative to adjuvant high-dose-rate (HDR) brachytherapy in early endometrial cancer patients.

PURPOSE: To evaluate the role of intensity-modulated radiation treatment (IMRT) as an alternative to high-dose-rate (HDR) brachytherapy in the treatment of the vagina in postoperative early endometrial cancer patients after surgery. METHODS AND MATERIALS: Planning computed tomography (CT) scans of 10 patients previously treated with HDR were used in this study. In all cases, a dose of 700 cGy/fraction was prescribed at a distance of 0.5 cm from the cylinder surface. The same CT scans were then used in IMRT planning. In this paradigm, the vaginal cylinder represents a component of a hypothetical immobilization system that would be indexed to the linac treatment table. RESULTS: Our study showed that IMRT provided relatively lower rectal doses than HDR when treatment was prescribed at a distance of 0.5 cm away from the cylinder surface. Maximum rectal doses were lower with IMRT compared with HDR (average: 89.0% vs. 142.6%, respectively, p < 0.05). Moreover, the mean rectal dose was lower in IMRT plans compared with HDR plans with treatment prescribed either to the surface (average: 14.8% vs. 21.4%, respectively, p < 0.05) or to 0.5 cm (average: 19.6% vs. 33.5%, respectively, p < 0.05). IMRT plans had planning target volume (PTV) coverage comparable with HDR (average PTV minimum for treatment prescribed to 0.5 cm: 93.9% vs. 92.1%, p = 0.71, respectively) with less inhomogeneity (average PTV maximum: 110.8% vs. 381.6%, p < 0.05). CONCLUSION: Our dosimetric analysis suggests that when used in conjunction with a suitable immobilization system, IMRT may provide an alternative to HDR brachytherapy in women with early endometrial cancer after hysterectomy. However, more studies are needed to evaluate the clinical merit of the IMRT in these patients.

[Intracavitary 500KHZ hyperthermia treatment of patients with endometrial and cervical cancer--preliminary clinical and pathological results]. / Wstepne wyniki zastosowania sródjamowej hipertermii 500 kHz u chorych na raka szyjki i trzonu macicy--ocena kliniczna i patologiczna.

Therapeutic effectiveness of elevated temperature is a well known issue. However raising the temperature inside the tumor sparing concurrently surrounding healthy tissue is not an easy task. Intracavitary, radiofrequency hyperthermia in uterine tumor cases allows to obtain elevated temperature in a simple, effective and safe way. Hyperthermic procedure was performed in 30 patients with cervical and endometrial cancer. In 10 cases it was a part of standard radiotherapy, in 20 hyperthermia proceeded radical surgery. A computer--controlled 300W amplifier and generator was used. Energy was transmitted via a modified Fletcher--type applicator. One or two 45-60 minute lasting sessions, with temperature reaching 46-49 degrees C were performed in each case. No severe side effects were seen. In a group where surgery was performed a characteristic temperature-induced changes were observed on tissue and cellular level. Higher number of performed procedures will be a base for randomized trials and, in the future enables us to incorporate hyperthermia into standard radiotherapy.

[The modern organ- and function-sparing surgical treatment in oncology]. / Sovremennoe organosokhraniaiushchee i funktsional'no shchadiashchee khirurgicheskoe lechenie v onkologii.

The results of organ-sparing treatment of patients with cancers of the breast, uterine cervix, endometrium and ovary are described in the paper. A prospective randomized clinical study launched in 1995 at Petrov's Research Institute of Oncology comprised cases of above 700 patients with breast cancer, around 300 women with cancer in situ and with microinvasive cancer of the uterine cervix and 83 patients with initial endometrial cancer. The results of the above treatment (segment resection + axillar dissection + radiotherapy) were shown to be similar to those obtained after Petey-Dyson mastectomy (5-year survival of 86.7% versus 88.8%, p = 0.81). The risk of local recurrence was increasing in patients with the tumors' diameter of more than 1 cm who were not treated by radiotherapy. The total regression of tumors was registered in 70% of patients with initial endometrial cancer after hormone therapy by progestagens and antiestrogens; 20% of them maintained the reproductive function.

[Experience with tantum rosa treatment for the prevention and management of radiation-induced proctitis and vaginitis in uterine and vaginal cancer]. / Opyt ispol'zovaniia preparata tantum roza pri profilaktike i lechenii luchevykh rektitov i vaginitov u bol'nykh rakom matki i vlagalishcha.

The investigation has been concerned with the efficacy of Tantum Rosa (Angelini Francesco, Italy) in the prevention (21) and therapy (87) of early- and late-onset radiation injuries of the rectum and vagina in patients exposed to radiation for cervical, uterine or vaginal carcinoma. Rectal tenesmus and pain subsided following 3-4 administrations at early stages of radiation rectitis. Intestinal discomfort was avoided when Tantum Rosa was used for prophylaxis. Therapeutic effect was reported after 7-10 administrations for moderate radiation vaginitis. Therapy for pannicular epithelite lasted less than two weeks.

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the endometrium.

PURPOSE: To develop recommendations for use of high-dose-rate (HDR) brachytherapy in patients with endometrial cancer. METHODS: A panel of members of the American Brachytherapy Society (ABS) performed a literature review, supplemented their clinical experience, and formulated recommendations for endometrial HDR brachytherapy. RESULTS: The ABS endorses the National Comprehensive Cancer Network (NCCN) guidelines for indications for radiation therapy for patients with endometrial cancer and the guidelines on HDR quality assurance of the American Association on Physicists in Medicine (AAPM). The ABS made specific recommendations for HDR applicator selection, insertion techniques, target volume definition, dose fractionation, and specifications for postoperative adjuvant vaginal cuff therapy, for vaginal recurrences, and for medically inoperable primary endometrial cancer patients. The ABS recommends that applicator selection should be based on patient and target volume geometry. The dose prescription point should be clearly specified. The treatment plan should be optimized to conform to the target volume whenever possible while recognizing the limitations of computer optimization. Suggested doses were tabulated for treatment with HDR alone, and in combination with external beam radiation therapy (EBRT), when applicable. For intravaginal brachytherapy, the largest diameter applicator should be selected to ensure close mucosal apposition. Doses should be reported both at the vaginal surface and at 0.5-cm depth irrespective of the dose prescription point. For vaginal recurrences, intracavitary brachytherapy should be restricted to patients with nonbulky (< 0.5-cm thick) disease. Patients with bulky (> 0.5-cm thick) recurrences should be treated with interstitial techniques. For medically inoperable patients, an appropriate applicator that will allow adequate irradiation of the entire uterus should be selected. CONCLUSION: Recommendations are made for HDR brachytherapy for endometrial cancer. Practitioners and cooperative groups are encouraged to use these recommendations to formulate their treatment and dose reporting policies. This will lead to meaningful comparisons of reports from different institutions and lead to advances and appropriate use of HDR.

Pelvic fractures following irradiation of endometrial and vaginal cancers-a case series and review of literature.

PURPOSE: To review the induction of pelvic fractures as a result of radiation therapy and to assess their management. MATERIALS AND METHODS: The charts of patients with endometrial and vaginal cancers irradiated between 1991 and 1995 were reviewed. All patients were treated with megavoltage machines, energy ranging from cobalt to 25 MV photons. RESULTS: We treated 336 patients, with a median follow-up duration of 28.9 months (range 0-73.3). Sixteen patients had symptomatic pelvic fractures. The 5-year actuarial incidence of symptomatic pelvic fracture was 2.1%. All patients had pain as the first symptom. The median time of onset was 11 months (range 4-46). Imaging studies of 37.5% (6/16) were initially interpreted to be recurrent malignancy. All patients were managed conservatively and nine patients showed radiological evidence of healing over a median time of 13 months (range 2-34). Six patients had specific drug treatment including provera, premarin, calcium supplements, or pamidronate. Of these, five healed. For the ten patients who did not have any specific treatment, only four showed signs of healing at the time of last follow-up. There was a trend toward earlier healing with specific drug treatment (P=0.11). CONCLUSIONS: Fractures can easily be mistaken for metastatic lesions (37.5% in this series) which might be treated with further irradiation. Although not statistically significant, there was a trend towards early healing with drug therapy. More studies are required to generate quantitative data for dose-response relationships and to evaluate the effect of drug therapy on the healing of such fractures.

Postoperative radiotherapy for endometrial carcinoma. Stage I. Wide variation in referral patterns but no effect on long-term survival in a retrospective study in the southeast Netherlands.

The aim of this study was to assess the referral pattern and the impact on long-term survival of postoperative radiotherapy in patients with adenocarcinoma of the endometrium stage I. This was a retrospective study performed in a regional cancer registry which covers a population of approximately 1,000,000 persons. All 724 patients registered between 1975 and 1992 in the Comprehensive Cancer Centre South, Eastern Section, The Netherlands, were analysed. All patients had received surgery as primary treatment which was performed in one of the seven community hospitals of the region. Radiotherapy was given in one regional department. All pathology reports were checked for data on tumour differentiation and myometrial invasion. Almost half the patients (45%) were referred for postoperative radiotherapy. The depth of myometrial invasion and the degree of tumour differentiation were the main factors (P < 0.0001) influencing referral for postoperative radiotherapy. The referral pattern varied between the different hospitals, but became more similar during 1985-1988, to diverge again in recent years. In patients younger than 60 years, the depth of myometrial invasion was significantly (P = 0.01) correlated with survival. In patients older than 60 years, tumour differentiation (P = 0.05) and age (P < 0.001) were correlated with survival, but not the depth of myometrial invasion. After adjustment for known prognostic factors, a survival benefit of postoperative radiotherapy could not be established. The studied group had an excess death rate over the normal Dutch female population. This excess death rate did not decrease during follow-up, as even after 10 years an excess death rate was found. A prospective randomised trial is ongoing in The Netherlands.