Management of tumor volume changes during preoperative radiotherapy for extremity soft tissue sarcoma: a new strategy of adaptive radiotherapy.

BACKGROUND: Using adaptive radiotherapy (ART), to determine objective clinical criteria that identify extremity soft tissue sarcoma (ESTS) patients requiring adaptation of their preoperative radiotherapy (RT) plan. PATIENTS AND METHODS: We included 17 patients with a lower extremity ESTS treated between 2019 and 2021 with preoperative RT, using helicoidal intensity-modulated RT (IMRT) tomotherapy, before surgical resection. We collected clinical, tumor parameters and treatment data. Repositioning was ascertained by daily Megavoltage computed tomography (MVCT) imaging. Using the PreciseART technology we retrospectively manually delineated at least one MVCT for each patient per week and recorded volume and dosimetric parameters. A greater than 5% change between target volume and planned target volume (PTV) dosimetric coverage from the initial planning CT scan to at least one MVCT was defined as clinically significant. RESULTS: All 17 patients experienced significant tumor volume changes during treatment; 7 tumors grew (41%) and 10 shrank (59%). Three patients (18%), all undifferentiated pleomorphic sarcomas (UPS) with increased volume changes, experienced significant reductions in tumor dose coverage. Seven patients required a plan adaptation, as determined by practical criteria applied in our departmental practice. Among these patients, only one ultimately experienced a significant change in PTV coverage. Three patients had a PTV decrease of coverage. Among them, 2 did not receive plan adaptation according our criteria. None of the patients with decreased tumor volumes had reduced target volume coverage. Monitoring volume variations by estimating gross tumor volume (GTV) on MVCT, in addition to axial and sagittal linear tumor dimensions, appeared to be most effective for detecting reductions in PTV coverage throughout treatment. CONCLUSIONS: Variations in ESTS volume are evident during preoperative RT, but significant dosimetric variations are rare. Specific attention should be paid to grade 2-3 UPSs during the first 2 weeks of treatment. In the absence of dedicated software in routine clinical practice, monitoring of tumor volume changes by estimating GTV may represent a useful strategy for identifying patients whose treatment needs to be replanned.

Effect of medical treatments in disseminated peritoneal leiomyomatosis: a case report.

Disseminated peritoneal leiomyomatosis (DPL) is a rare gynecologic disease involving multifocal proliferation of myomas. The pathogenesis remains unclear. Although there is no standard treatment, medical therapies have attempted to suppress estrogen levels by using gonadotrophin-releasing hormone agonist and aromatase inhibitor (AI) therapy with differing degrees of success. Surgery is also an option in symptomatic patients, and in the event of partial or no response to medical treatments. We report a case of DPL in a young woman with a previous history of myomectomy. She was treated sequentially with ulipristal acetate and AI.

Breast desmoid tumor management in France: toward a new strategy.

PURPOSE: Desmoid tumors (DTs) are rare tumors that originate from myofibroblastic tissue. Recently, initial wait and see was recommended (ESMO guidelines Ann Oncol 2017) in the most frequent locations. This study investigates the outcome of breast desmoid tumor (BDT) according to the initial strategy. METHOD: Data from all consecutive patients treated from a BDT in four referral centers were collected. Only intra-mammary desmoid tumors were included. A pathological review and a molecular analysis (CTNNB1 gene mutation) were performed (National re-reading network of sarcomas-RRePS). Patients were grouped according to initial strategy: surgery group (SG) and active surveillance group (ASG). RESULTS: A total of 63 patients (61 women, 2 men) met the inclusion criteria. Median age was 50 years (16-86). CTNNB1 mutation was found in 61% (n = 36). SG included 46 patients (73%) (41 partial mastectomies, 2 mastectomies, and 3 mastectomies associated to parietectomies). Surgical margins were positive in 15 patients (33.3%). Median follow-up of SG was 24.9 (0.5-209) months; and 4 patients (8.7%) developed recurrence. ASG included 17 patients (27%). Their median follow-up was 42.2 (0-214) months, and 15 patients (88.2%) did not require any additional treatment. Six patients (35%) had a spontaneous regression, 9 patients (52%) were stable, and 2 patients presented a significant progression that was treated by partial mastectomy. CONCLUSION: This study supports an initial nonsurgical approach to BDTs followed by surgery based on tumor growth in select cases, which is consistent with current ESMO recommendations.

Left Lateral Endosurgical Extraperitoneal Total Hysterectomy with Para-Aortic and Pelvic Lymphadenectomy: A Novel Approach for the Obese Patient with Endometrial Cancer.

STUDY OBJECTIVE: To describe the left lateral extraperitoneal approach to perform complete para-aortic and pelvic lymphadenectomy and transverse total hysterectomy from left to right as a novel approach to treat obese patients with endometrial cancer. Laparoscopic management of obese patients represents a challenge for the gynecologic surgeon. The extraperitoneal approach is technically easier in the obese patient because it naturally creates a bowel-free operative field. DESIGN: A prospective pilot bicentric and descriptive study (Canadian Task Force classification III) evaluating the feasibility and reproducibility of the transverse total hysterectomy and complete lymphadenectomy through left endoscopic extraperitoneal approach in obese patients with endometrial cancer. SETTING: A comprehensive cancer center in Toulouse and a teaching university hospital in Madrid. PATIENTS: Sixteen consecutive overweight or obese patients (body mass index > 25 kg/m2) with high-risk endometrial cancer. INTERVENTIONS: Currently, the left extraperitoneal approach is routinely used to perform complete para-aortic and pelvic lymphadenectomy. It provides direct access to the left ureter and uterine pedicle. This access can be extended to the right side when performing a transverse extrafascial hysterectomy from left to right. The procedure starts from the left extraperitoneal space, where the left uterine artery is sectioned and the vesicovaginal and rectovaginal septa are developed, without opening the peritoneum. Colpotomy is performed from the left to the right side. Once the right ureter is identified, the right uterine artery can be safely transected. Alternatively, the right uterine artery can be sealed and sectioned during the right pelvic lymphadenectomy. At the end of the procedure the peritoneum is opened to complete the surgery. MEASUREMENTS AND MAIN RESULTS: Between May 2015 and February 2016, 16 consecutive obese patients were successfully treated using this technique. Median patient age was 62 years (range, 44-78), and median body mass index was 32.5 kg/m2 (range, 26-42). In 3 cases the right uterine artery was sealed during the right pelvic lymphadenectomy, in 11 cases after completing vaginal opening, and in 2 cases after peritoneal opening. The median operative time was 137.5 minutes (range, 66-260). The median blood loss was 85 mL (range, 0-260), and no blood transfusion was required in any of our 16 patients. No significant complications occurred. CONCLUSION: The full extraperitoneal approach represents an interesting alternative strategy for the surgical treatment of obese patients with high-risk endometrial cancer.

Vaginal reconstruction with pedicled vertical deep inferior epigastric perforator flap (diep) after pelvic exenteration. A consecutive case series.

Vaginal reconstruction after pelvic exenteration (PE) represents a challenge for the oncologic surgeon. Since the introduction of perforator flaps, using pedicled vertical DIEP (deep inferior epigastric perforator) flap allows to reduce the donor site complication rate. From November 2012 to December 2014, 27 PEs were performed in our institution. 13 patients who underwent PE with vaginal reconstruction and programmed DIEP procedure for gynecologic malignancies were registered. Nine patients underwent PE for recurrent disease and four for primary treatment. Six of the 13 patients have a preoperative fistula. Anterior PE was performed in 10 patients, and total PE in 3 patients. A vertical DIEP flap was performed in 10 patients using one or two medial perforators. The reasons for abortion of vertical DIEP flap procedure were: failure to localizing perforator vessels in two cases, and unavailability of plastic surgeon in one case. A vertical fascia-sparring rectus abdominis myocutaneous flap was then harvested. Median length of surgery was 335min, and 60min for DIEP harvesting and vaginal reconstruction. No flap necrosis occurred. One patient in the VRAM (vertical rectus abdominis myocutaneous) group experienced a late incisional hernia and one patient in the DIEP flap group required revision for vaginal stenosis. In our experience, DIEP flap represents our preferred choice of flap for circumferential vaginal reconstruction after PE. To achieve a high reproducibility, the technically demanding pedicled vertical DIEP flap has to be harvested by a trained surgeon, after strict evaluation of the preoperative imaging with identification and localization of perforator vessels.

Doxorubicin and ifosfamide for high-grade sarcoma during pregnancy.

PURPOSE: Doxorubicin and ifosfamide are highly active drugs for the treatment of high-grade sarcomas, but little is known on the optimal management of young patients who develop such malignancies during pregnancy. METHODS: We report on a single-institution series of patients (n = 9) with high-grade sarcoma diagnosed during the third trimester of pregnancy. Neoadjuvant chemotherapy combining doxorubicin (50 mg/m(2) day 1) and ifosfamide (2.5 g/m(2) days 1-2) with standard mesna rescue every 3 weeks was administered during the third trimester of pregnancy in five patients. RESULTS: We observed a favourable outcome for both the mother and the offspring in all cases. Maternal and neonatal pharmacokinetic data for ifosfamide were obtained from one patient and did not evidence a transplacental transfer of this drug. The use of other active drugs (cisplatin, etoposide, dactinomycin and cyclophosphamide) in sarcoma during pregnancy is discussed on the basis of a comprehensive review of the English literature. CONCLUSIONS: In view of this single-centre experience, we suggest that the treatment of high-grade sarcoma during the third trimester of pregnancy should include an adapted regimen tailored to the pharmacological specificities of the pregnant patients.

Accuracy of diffusion-weighted echo-planar MR imaging and ADC mapping in the evaluation of residual cervical carcinoma after radiation therapy.

OBJECTIVES: The impact of diffusion-weighted imaging (DWI) and apparent diffusion coefficients (ADCs) of MR imaging on the evaluation of residual Uterine Cervical Carcinoma after Radiation Therapy, in addition to conventional MR images. METHODS: Fourty-nine women presenting with a uterine cervical cancer were examined with 1.5 T MRI and DWI, 8 (4-20) weeks after treatment. Treatment response was determined based on the histopathological results after therapy and was classified as a complete response (CR) or residual disease (RD). Post-treatment DWI and ADC results were compared. RESULTS: Five (11%) and 44 (89%) patients were considered as having histologically-proven RD or a CR respectively. The mean ADC of cervical tissue for all patients was 1.74±0.324×10(-3) mm(2)/s and the SD was 1.94±1.11×10(-4). The mean ADC was 1.62±0.21×10(-3) mm(2)/s (SD=1.45×10(-4)) for the 5 patients with RD versus 1.76±0.33×10(-3) mm(2)/s (SD=1.99×10(-4)) for the 44 patients with a CR (p=0.09). Using 1.7×10(-3) mm(2)/s as a radiological cut-off value for the ADC, all patients classified as having histologically-proven RD had a mean ADC of ≤1.7×10(-3). In 12 (25%) cases, RD was suspected on T2-weighted MRI images alone. Eight of these cases were considered as false positives compared to the histological results. Their mean ADC was 1.98×10(-3) mm(2)/s and none of them had an ADC of <1.7×10(-3) mm(2)/s. CONCLUSION: Although our results were not statistically significant, ADC values could potentially be used to predict and monitor the response of uterine cervical cancer.

Interest of diffusion-weighted echo-planar MR imaging and apparent diffusion coefficient mapping in gynecological malignancies: a review.

Magnetic resonance imaging (MRI) remains the standard modality for the local staging of gynecological malignancies but it has several limitations, particularly for lymph node staging or evaluating peritoneal carcinomatosis. Consequently, there has been a growing interest in functional imaging modalities. Based on molecular diffusion, diffusion-weighted imaging (DWI) is a unique, noninvasive modality that provides excellent tissue contrast and was shown to improve the radiological diagnosis of malignant tumors. Using quantitative apparent diffusion coefficient (ADC) measurement of DWI provides a new tool for better distinguishing malignant tissues from benign tumors. The aim of the present review is to report on the results of DWI for the assessment of patients with gynecological malignancies. An analysis of the literature suggests that DWI studies would improve the diagnosis of cervical and endometrial tumors. It may also improve the assessment of tumor extension in patients with peritoneal carcinomatosis from gynecological malignancies. However, since the signal intensity of some cancers can range from high intensity to low intensity, a degree of uncertainty was demonstrated due to the proximity of the normal uterine myometrium and ovaries. Interestingly, there is also evidence that ADC might improve the follow-up and monitoring of patients who receive anticancer therapies, including chemotherapy or radiation therapy.

Feasibility of metronomic oral cyclophosphamide plus prednisolone in elderly patients with inoperable or metastatic soft tissue sarcoma.

BACKGROUND: The number of elderly people with soft tissue sarcoma (STS) is increasing. A sizeable population of elderly patients with STS is unfit for conventional doxorubicin- or ifosfamide-based chemotherapy. We assessed the feasibility of metronomic oral cyclophosphamide (CPM) in this population. PATIENTS AND METHODS: Patients aged 65 years or older with unresectable STS received CPM 100mg twice daily plus prednisolone 20mg daily, the first week of a 2-week cycle in the outpatient setting. Main evaluation criterion was safety. Secondary evaluation criteria were objective response rate and progression-free survival. RESULTS: Twenty-six patients (median age: 72, range 66-88) received a total of 330 cycles (median per patient: 10, range 2-41) as first (n=19) or second-line chemotherapy (n=7). The most frequent histological subtypes were poorly differentiated sarcoma (n=8), leiomyosarcoma and liposarcoma (n = 5 each) and angiosarcoma (n=3). Grade ≥3 lymphopenia was observed in 81% of pts but no opportunist infection occurred. Grade 3 anaemia and thrombocytopenia occurred in 2 pts (8%) each. No other grade 3-4 toxicity was seen. The response rate was 26.9% (95%CI: 9.9-44.0) and the disease control rate (responses and stable disease >12 weeks) was 69.2% (95%CI: 51.5-87.0). One complete (hepatic epithelioid haemangio-endothelioma) and 6 partial responses (including 5pts with radiation-induced sarcomas) were seen. Progression-free survival ranged from 0 to 20.6 months (median: 6.8 months) and was significantly longer in patients with radiation-induced sarcomas (median: 7.8 versus 5.2 months, p=0.02). CONCLUSION: Metronomic CPM showed good safety results for this frail population, with promising activity in patients with radiation-induced sarcoma. Toxicity profile was favourable, allowing prolonged home staying and rare treatment discontinuations. A larger prospective study is warranted to confirm these encouraging results in elderly with STS.

Hyperthermic isolated limb perfusion in locally advanced soft tissue sarcoma and progressive desmoid-type fibromatosis with TNF 1 mg and melphalan (T1-M HILP) is safe and efficient.

BACKGROUND: In a prior randomized phase II trial comparing hyperthermic isolated limb perfusion (HILP) with four different doses of tumor necrosis factor alpha (TNF-alpha), no dose effect was detected for response, but systemic toxicity was far lower with low-dose TNF-alpha. The objective of the present study was to confirm these data on a larger sample size of locally advanced or recurrent extremity soft tissue sarcomas with low-dose TNF-alpha. METHODS: We assessed a prospective database comprising 100 HILP (38-40 degrees C) with melphalan (10 mg/L) and TNF-alpha (1 mg). The remnant tumor was resected 2 months later. RESULTS: Among 52 recurrences, 18 were in a previously irradiated field. Stages according to the American Joint Committee on Cancer classification were II (19 patients), III (78 patients), and IV (3 patients). The site/size were: 30 patients/57 mm and 70 patients/86 mm for the upper and lower limbs, respectively. Tumor grades (FNCLCC) were 1 (23 patients), 2 (34 patients), and 3 (43 patients). Fifty-one patients had received systemic chemotherapy before HILP. Responses on magnetic resonance imaging were 30% complete, 49% partial, 9% no change, and 12% progression. No mortality or systemic toxicity occurred. Local toxicity (Wieberdink) attained grade 2 (16 patients), 3 (5 patients), and 4 (1 patient). Limbs were able to be saved in 87% patients. Three-year overall survival and the local recurrence rate were 89% and 18%, respectively. Age, sex, tumor size, recurrence, uni- or multifocality, grade, preoperative chemotherapy, and a previously irradiated field were not predictive of response or local toxicity. CONCLUSIONS: We confirm that 1 mg of TNF-alpha is as effective as the standard dose and results in no systemic toxicity.