A. Rovirosa

Impact of radiotherapy on local control and survival in uterine sarcomas: a retrospective study from the Grup Oncologic Català-Occità.

PURPOSE In order to provide more information for the clinician and to analyze the impact of radiation therapy on the loco-regional disease-free interval (LRFI), disease-free interval (DFI) and specific overall survival (OS), a multicentric retrospective study of uterine sarcomas has been undertaken using cases reported to the Grup Oncològic Català-Occità (GOCO). PATIENTS AND METHODS One hundred three patients were selected for this study with a median follow-up period of 49 months. Patients were restaged using the FIGO classification for endometrial adenocarcinoma. Radiotherapy was administered postoperatively to the entire pelvis in 52% of cases (54/103) and was combined with brachytherapy in 24 patients. Mean given dose was 48 Gy, with a 95% confidence interval of 45 to 50 Gy. Variables have been tested for homogeneity between hospitals. Univariate and multivariate analyses have also been carried out. RESULTS Mean age of the selected patients was 59 years (range 35-84). Stages were distributed as follows: 66 patients (64%) in Stage I; 16 in Stage II (15.5%); 12 in Stage III (11.5%); 9 patients in Stage IVa (9%). Pathological distribution was 41.5% leiomyosarcoma, 39% mixed Mullerian tumours, 16.5% stromal sarcomas, and 2.9% of a miscellaneous group. Overall survival for the entire group was 63.7% and 56% at 2 and 5 years, respectively. Probability of LRFI reached 59.8% at 2 years and 57.4 at 5 years. The DFI at 2 and 5 years were 52.9 % and 48.7%, respectively. The LRFI probability was 41% and 36% at 2 and 5 years, respectively, without radiotherapy and reached 76% at 2 and 5 years among those patients treated with radiotherapy. There was also an increase in DFI probability because of the effect of radiotherapy, from 35% to 68.5% and from 33% to 53% at 2 and 5 years, respectively. The overall survival probability for patients treated with radiotherapy was 76% and 73% at 2 and 5 years, respectively and 51% at 2 years and 37% at 5 years without radiotherapy. Multivariate analysis demonstrated that radiotherapy improved LRFI, DFI, and overall survival. CONCLUSION We conclude that postoperative radiotherapy in our series of patients diagnosed with uterine sarcoma has an impact on loco-regional and disease-free progression intervals and survival.

Prospective evaluation of squamous cell carcinoma and carcinoembryonic antigen as prognostic factors in patients with cervical cancer.

Carcinoembryonic antigen (CEA) and squamous cell carcinoma(SCC) serum levels were prospectively determined in 159 untreated patients diagnosed with carcinoma of the uterine cervix from 1991 to 2001. The histological analysis showed epidermoid cancer in 117 patients, adenocarcinoma in 26 patients, adenosquamous carcinoma in 12 patients and other histological types in the remaining 4 patients. Tumor marker sensitivity was related to the histological type with abnormal SCC (>2 ng/ml) in 51.3% of squamous tumors in contrast to the 7.1% found in other histologies. By contrast, CEA sensitivity was not related to histology with abnormal values (>5 ng/ml) in 25% of squamous tumors, 19% of adenocarcinomas, 33% of adenosquamous carcinomas and 25% of other histologies. CEA and SCC serum levels were clearly related to tumor stage, parametrial invasion, tumor size and nodal involvement. Elevated pretreatment CEA indicates parametrial invasion with a probability of 82%. Likewise, pretreatment CEA and SCC serum levels were of prognostic value, with a shorter disease-free survival and overall survival in patients with abnormal levels. All patients with adenocarcinomas and abnormal CEA had relapse during follow-up. Multivariate analysis indicated that parametrial invasion, age, tumor size and SCC were independent prognostic factors. In conclusion, CEA and SCC are useful tumor markers in carcinomas of the uterine cervix, with a clear relationship with well-known prognostic factors (parametrial invasion, nodal involvement), and are of prognostic value.

Anti-inflammatory effects of low-dose radiotherapy: Indications, dose and radiobiological mechanisms involved

Low-dose radiotherapy (LD-RT) has been used for several benign diseases, including arthrodegenerative and inflammatory pathologies. Despite its effectiveness in clinical practice, little is known about the mechanisms through which LD-RT modulates the various phases of the inflammatory response and about the optimal dose fractionation. The objective of this review is to deepen knowledge about the most effective LD-RT treatment schedule and radiobiological mechanisms underlying the anti-inflammatory effects of LD-RT in various in vitro experiments, in vivo studies, and clinical studies.ZusammenfassungNiedrigdosierte Strahlentherapie (LD-RT) wird für die Behandlung verschiedener gutartiger Erkrankungen, einschließlich für arthrodegenerative und entzündliche Erkrankungen verwendet. Obwohl diese in der Praxis effektiv sind, wissen wir noch sehr wenig über die zugrundeliegenden Mechanismen der entzündungshemmenden Wirkung und die optimale Dosisfraktionierung. Das Ziel des Artikels ist es, unser Wissen über LD-RT und die zugrundeliegenden entzündungshemmenden Effekte in verschiedenen In-vitro-Versuchen und In-vivo-Studien sowie in klinischen Studien zu vertiefen.

Anti-inflammatory effects of low-dose radiotherapy

Low-dose radiotherapy (LD-RT) has been used for several benign diseases, including arthrodegenerative and inflammatory pathologies. Despite its effectiveness in clinical practice, little is known about the mechanisms through which LD-RT modulates the various phases of the inflammatory response and about the optimal dose fractionation. The objective of this review is to deepen knowledge about the most effective LD-RT treatment schedule and radiobiological mechanisms underlying the anti-inflammatory effects of LD-RT in various in vitro experiments, in vivo studies, and clinical studies.ZusammenfassungNiedrigdosierte Strahlentherapie (LD-RT) wird für die Behandlung verschiedener gutartiger Erkrankungen, einschließlich für arthrodegenerative und entzündliche Erkrankungen verwendet. Obwohl diese in der Praxis effektiv sind, wissen wir noch sehr wenig über die zugrundeliegenden Mechanismen der entzündungshemmenden Wirkung und die optimale Dosisfraktionierung. Das Ziel des Artikels ist es, unser Wissen über LD-RT und die zugrundeliegenden entzündungshemmenden Effekte in verschiedenen In-vitro-Versuchen und In-vivo-Studien sowie in klinischen Studien zu vertiefen.

M-CAVI, a neoadjuvant carboplatin-based regimen for the treatment of T2-4N0M0 carcinoma of the bladder.

Carboplatin, methotrexate, and vinblastine (M-CAVI) is an active and well-tolerated regimen for bladder cancer patients ineligible for cisplatin-based regimens. We treated 47 T2-4 N0 M0 bladder cancer patients with M-CAVI in a neoadjuvant phase II trial. These 47 patients are evaluable for clinical response and toxicity. Clinical overall response rate was 34%, for a 95% confidence interval (CI95%) of 21-49%. Pathological response was seen in 40% of the patients (CI95%, 26-56%) with a 26.5% rate of pathological complete response (CI95%, 15-42%). Factors associated with the achievement of a response to therapy were the initial TNM stage (pT3a or lower, greater than pT3a, p = 0.001) and a Karnofsky score greater or equal than 90%, which was marginally significant (p = 0.08). With a median follow-up of 14 months, the disease-specific actuarial survival at 2 years is 42%. No patient has relapsed beyond 21 months of follow-up in a disease-free status. Toxic effects have been moderate. In conclusion, M-CAVI is an active and well-tolerated regimen that should be compared in terms of response rate and survival with a cisplatin-based regimen for invasive bladder cancer.

Cavitary Pulmonary Metastases in Transitional Cell Carcinoma of the Urinary Bladder

About 4% of metastases to the lung eventually evolve into cavitary lesions. The origin of these lesions are squamous cell carcinomas in 69% of cases and adenocarcinomas in the rest. Lung metastases develop in 20% of patients with transitional cell carcinomas of the urinary bladder (TCB), usually as multiple nodules. The cavitation of these metastases is an unusual finding, and a review of the literature has revealed only 7 cases of cavitary metastatic lesions from TCB. We add 2 further cases with cavitary metastases and study their clinical and radiographic features, in comparison with those previously described in the literature.

Hypofractionated high-dose-rate plesiotherapy in nonmelanoma skin cancer treatment.

PURPOSE Nonmelanoma skin cancer (NMSC) is the commonest cancer in humans. NMSC treatment currently includes surgery, radiation therapy, and topical approaches. The objective was to analyze and compare the outcomes, toxicity, and cosmesis of NMSC treated by two hypofractionated high-dose-rate (HDR) plesiotherapy techniques. METHODS AND MATERIALS A retrospective institutional clinical study of 134 basal cell or squamous cell skin carcinomas treated at Radiation Oncology Department. Lesions were treated from November 2006 to December 2011 with a moderate hypofractionated HDR plesiotherapy using a fixed applicator or a customized mold. RESULTS After a median follow-up of 33 months, overall disease-free survival at 3 and 5 years was 95.12% and 93.36%, respectively. For Leipzig applicator, disease-free survival at 3 years was 94.9% and 94.9% at 5 years, for customized mold was 93.1% at 3 years and 88% at 5 years. Complete regression was achieved in 98% of lesions. Two lesions persisted after treatment; both had been treated by a Leipzig applicator. Six lesions suffered local recurrence (five Leipzig applicators and three molds, p = 0.404). Grade <2 acute toxicity noted in 57.3% of patients. Only 2.2% of lesions had Grade 4 acute toxicity. Borderline significant increase of toxicity was associated with customized molds (p = 0.067). Larger tumors were associated with higher acute skin toxicity. The cosmesis outcomes were excellent or good in 82% of patients, fair in 13%, and not available in 5%. CONCLUSIONS Hypofractionated HDR plesiotherapy is an effective and well-tolerated treatment for NMSC with different toxicity levels depending on the plesiotherapy technique used.

Consensus on treatment of endometrium carcinoma with brachytherapy

Radiotherapy (RT) is commonly used as adjuvant treatment following hysterectomy and double oophorectomy in endometrial carcinoma. Prophylactic vaginal brachytherapy (BT) is the most common treatment in BT units. The PORTEC and GOG 99 studies have attempted to clarify the indications of BT and postoperative external RT, changing treatment standards. However, prophylactic BT regimens are very varied and there is currently no consensus on how to treat patients in terms of dose per fraction and number of fractions. Moreover, unoperated cases of endometrium are uncommon and there is limited experience in their treatment with BT. The 9th Consensus Meeting of the SEOR and SEFM Brachytherapy Group, held in Malaga on 11 March 2011, was therefore dedicated to “Brachytherapy in Endometrial Carcinoma”. This article presents the consensus on treatment of endometrial carcinoma in operated (prophylactic vaginal BT) and unoperated (endouterine BT) patients.

Is anti-inflammatory radiotherapy an effective treatment in trochanteritis?

OBJECTIVE To evaluate the analgesic efficacy of low-dose radiotherapy in refractory cases of trochanteritis. METHODS We evaluated a total of 60 consecutive patients who received low-dose radiotherapy to achieve an anti-inflammatory and analgesic effect for recurrent trochanteritis following scarce response to conventional therapy. All patients were evaluated at baseline (prior to radiotherapy) and at 1 and 4 months after radiotherapy and then yearly thereafter for pain assessment using a visual analogue scale (VAS) and to determine the administration of analgesic treatment. RESULTS An improvement in the symptomatology was observed in 62% of the patients with a significant reduction in the VAS (8 ± 2 vs 4 ± 2; p < 0.0001), which was largely maintained until the second evaluation at 4 months. In the cases responding to radiotherapy, the probability of maintaining improvement beyond 24 months was 70%. CONCLUSION Low-dose anti-inflammatory radiation may be used in the treatment of the recurrent cases of relapse or no response of trochanteritis to conventional treatments, with a high probability of remission of pain. These preliminary results indicate the need for evaluating the use of radiotherapy in patients with trochanteritis refractory to conventional treatment in a long-term controlled study. Advances in knowledge: Radiotherapy provides effective analgesic treatment for patients refractory to standard treatment for trochanteritis.

Phase I trial of sorafenib with concurrent radiotherapy (RT) in patients with invasive bladder cancer treated with bladder-sparing intent: A Spanish Oncology Genitourinary Group study.

270 Background: Preclinical studies suggest enhanced radiation-induced cell death when VEGFR inhibitor therapies are combined with RT. METHODS Patients with localized muscle invasive urothelial carcinoma of the bladder in clinical stage T2-3 N0 M0, who were not eligible or rejected radical cystectomy, ECOG PS 0-2, and adequate hematological, renal and hepatic function, were enrolled in this phase I study to assess safety and identify the dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD) of sorafenib and RT. A 3+3 dose escalation design with cohorts of 3-6 patients was used. Treatment consisted of TUR, followed by normofractionated (2 Gy/day) external-beam RT with high-energy photons, 46 Gy to minor pelvis and 66 Gy to bladder, combined with sorafenib given po continuously. Sorafenib was started two weeks before RT and was administered for 12 weeks, finishing 4 weeks after RT. Dose levels 1, 2 and 3 corresponded to sorafenib 200 mg qd, 200 mg bid and 800 mg bid. Pathological response was assessed by post-treatment TUR. RESULTS Ten patients were included: median age 71 years (44-84); gender 7M: 3F. Patients were treated at 3 dose levels, the MTD was reached at level 3 and the RD was: sorafenib 200 mg bid with RT. Two DLTs occurred, both at the third dose level: diarrhea grade 3 and digestive bleeding grade 3 with secondary anemia and hemodynamic angor in a patient with previous small bowel angiodysplasia. The most frequent toxicity was diarrhea. Other grade 1-2 toxicities included rash, fatigue, hand-foot syndrome, hypertension, dysuria and urinary frequency. One patient developed late radiation cystitis. Pathological complete response was achieved in 8 of 9 patients evaluated. Salvage cystectomy has been performed in one patient due to recurrent superficial bladder tumor. After a median follow up of 30 months, 6 patients remain disease-free with intact bladder. CONCLUSIONS The combination of sorafenib and RT appears to be feasible and safe allowing long-term bladder preservation in selected patients. A phase II study to assess the activity of this promising combination is warranted.