Interval cytoredutive surgery and HIPEC in advanced ovarian cancer with small-bowel disease: results and reflections.

INTRODUCTION: Small-bowel involvement in patients with ovarian cancer has been strongly correlated with the possibility of cytoreduction and thus with survival. The main objective of this study was to evaluate the prognostic significance of small-bowel involvement in patients undergoing optimal-complete interval cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). METHODS: We included a series of patients diagnosed with stage IIIC-IVA (pleural effusion) high-grade serous epithelial ovarian cancer and in whom CRS + HIPEC was indicated after neoadjuvant systemic chemotherapy (NACT). The study period extended from January 2008 to January 2020, with a minimum follow-up of 12 months from the inclusion of the last patient. A multivariate analysis using Cox regression allowed us to identify the variables that were independently related to disease-free survival. RESULTS: A total of 144 patients were selected, 13 (9%) of whom were excluded from the analysis, because their disease was considered unresectable. The study included a series of 131 patients with a median age of 62 years (34-79 years) and a median Peritoneal Cancer Index (PCI) calculated during surgery of 9 (1-35). The median PCI of bowel areas 9-12 (SB-PCI) was 3 (1-10). Performance of a CC-1 cytoreduction (HR: 1.93, 95% CI: 1.02-3.64, p = 0.042) and SB-PCI greater than 3 (HR: 2.25, 95%CI: 1.13-4.48, p = 0.21) were independent factors associated with shorter disease-free survival. CONCLUSION: Small-bowel involvement, even in patients with a macroscopically complete resection, showed a correlation with worse prognostic outcomes and could be considered as a variable in the postoperative management of these patients.

Preoperative chemoradiotherapy for rectal cancer: randomized trial comparing oral uracil and tegafur and oral leucovorin vs. intravenous 5-fluorouracil and leucovorin.

PURPOSE: To compare, in a randomized trial, 5-fluorouracil (FU) plus leucovorin (LV) (FU+LV) vs. oral uracil and tegafur (UFT) plus LV (UFT+LV) given concomitantly with preoperative irradiation in patients with cT3-4 or N+ rectal cancer. METHODS AND MATERIALS: A total of 155 patients were entered onto the trial. Patients received pelvic radiotherapy (4500-5,040 cGy in 5 to 6 weeks) and chemotherapy consisting of two 5-day courses of 20 mg/m(2)/d LV and 350 mg/m(2)/d FU in the first and fifth weeks of radiotherapy (77 patients) or one course of 25 mg/d oral LV and 300 mg/m(2)/d UFT for 4 weeks beginning in the second week of radiotherapy (78 patients). The primary endpoints were pathologic complete response (pCR) and resectability rate. Secondary endpoints included downstaging rate, toxicity, and survival. RESULTS: Grade 3-5 acute hematologic toxicity occurred only with FU+LV (leukopenia 9%; p = 0.02). There were no differences in resectability rates (92.1% vs. 93.4%; p = 0.82). The pCR rate was 13.2% in both arms. Tumor downstaging was more frequent with UFT+LV (59.2% vs. 43.3%; p = 0.04). Three-year overall survival was 87% with FU+LV and 74% with UFT+LV (p = 0.37). The 3-year cumulative incidences of local recurrence were 7.5% and 8.9%, respectively (p = 0.619; relative risk, 1.46; 95% confidence interval 0.32-6.55). CONCLUSION: Although this study lacked statistical power to exclude clinically significant differences between both groups, the outcome of patients treated with UFT+LV did not differ significantly from that of patients treated with FU+LV, and hematologic toxicity was significantly lower in the experimental arm.

Radiochemotherapy with cisplatin and oral tegafur in advanced head and neck cancer: long-term results of a phase II study.

AIMS AND BACKGROUND: To evaluate the tolerance and efficacy of an original concurrent radiochemotherapy regimen in locally advanced head and neck cancer. METHODS: Sixty-four patients with stage III or IV squamous cell carcinoma arising from a head and neck mucosal site were eligible. Simultaneous radiochemotherapy consisted of two courses of continuous infusional cisplatin (20 mg/m2/d, days 1-4 and 29-32) and oral tegafur (1200 mg/d, days 1-14 and 29-43), together with conventional radiation therapy up to a total dose of 70-75 Gy over nine weeks. RESULTS: All the patients were evaluated for toxicity and response. Acute mucositis was the most prevalent complication. Grade 3 toxicities were mucositis (44%), skin toxicity (10%), leukopenia (8%), and thrombocytopenia (1%). No toxic death was observed. Complete response to treatment was observed in 72% of patients. With a median follow-up of 48.5 months (range, 27-84), 5-year actuarial rate of local-regional control, disease-free survival, overall survival and disease-specific survival were 60% (95% confidence interval [CI], 40-70%), 55% (95% CI, 45-65%), 51% (95% CI, 43-59%) and 61% (95% CI, 53-69%), respectively. CONCLUSIONS: Response, local-regional control and survival rates are equivalent to those reported from other concomitant radiochemotherapy combinations. However, the regimen offers the advantage of its tolerance and toxicity profile.

Sensivity to change of the Spanish validated Memorial Pain Assessment Card in cancer patients.

INTRODUCTION: Pain intensity is a good parameter to assess effective treatment of cancer and palliative care. The Memorial Pain Assessment Card (MPAC) is a quick, easy and reliable measure of quality of life in cancer patients. The MPAC was validated in Spanish in 2004. This study evaluated the sensitivity to change Spanish version of the MPAC. MATERIAL AND METHODS: An epidemiological, prospective, 1- month, multicentre study, conducted at 4 oncology services. Patients evaluated suffered chronic cancer pain and were in a susceptible situation of change. The MPAC was administrated at baseline, at one week and at one month, including the 4 subscales (pain relief [VASPR], pain intensity measured by VAS [VASPI] and by an 8-item descriptor [Tursky], and psychological distress [VASMOOD]). Satisfaction of patients and health-care professionals with the MPAC was also evaluated. RESULTS: A total of 54 patients were studied. All of the MPAC subscales showed sensitivity to change during the follow-up. The subscale values at visit 1 vs. visit 3 were: VASPR 4.5+/-1.9 vs. 6.3+/-2.3, VASPI 6.6+/-1.6 vs. 3.5+/-1.9 and VASMOOD 5.5+/-2.1 vs. 4.0+/-2.1). Patients and healthcare professionals agreed in the facility use MPAC card (63% and 71% of cases, respectively). CONCLUSIONS: The present study showed sensitivity to change among the different MPAC subscales of the Spanish version. Moreover, the MPAC Spanish version has proven to be a good tool accepted by health-care-professionals and patients. Due to its facility of administration, it may allow a useful and quick evaluation of cancer-related pain in the clinical practice.

Metastatic disease from chordoma.

Chordomas are tumors with a bad prognosis, because of their location, local aggressiveness and high rate of local relapse. Despite of be benign tumors, they have certain capacity of metastasize and a clinical evolution that results interesting. When we analyzed our series with 35 chordomas studied and treated between 1975 and 2002, we found three patients that experienced a systemic dissemination.

Interval cytoredutive surgery and HIPEC in advanced ovarian cancer with small-bowel disease: results and reflections

Introduction: Small-bowel involvement in patients with ovarian cancer has been strongly correlated with the possibility of cytoreduction and thus with survival. The main objective of this study was to evaluate the prognostic significance of small-bowel involvement in patients undergoing optimal-complete interval cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).Methods: We included a series of patients diagnosed with stage IIIC-IVA (pleural effusion) high-grade serous epithelial ovarian cancer and in whom CRS + HIPEC was indicated after neoadjuvant systemic chemotherapy (NACT). The study period extended from January 2008 to January 2020, with a minimum follow-up of 12 months from the inclusion of the last patient. A multivariate analysis using Cox regression allowed us to identify the variables that were independently related to disease-free survival.Results: A total of 144 patients were selected, 13 (9%) of whom were excluded from the analysis, because their disease was considered unresectable. The study included a series of 131 patients with a median age of 62 years (34-79 years) and a median Peritoneal Cancer Index (PCI) calculated during surgery of 9 (1-35). The median PCI of bowel areas 9-12 (SB-PCI) was 3 (1-10). Performance of a CC-1 cytoreduction (HR: 1.93, 95% CI: 1.02-3.64, p = 0.042) and SB-PCI greater than 3 (HR: 2.25, 95%CI: 1.13-4.48, p = 0.21) were independent factors associated with shorter disease-free survival.Conclusion: Small-bowel involvement, even in patients with a macroscopically complete resection, showed a correlation with worse prognostic outcomes and could be considered as a variable in the postoperative management of these patients. (AU)

Risk-adapted androgen deprivation and escalated three-dimensional conformal radiotherapy for prostate cancer: Does radiation dose influence outcome of patients treated with adjuvant androgen deprivation? A GICOR study.

PURPOSE: Multicenter study conducted to determine the impact on biochemical control and survival of risk-adapted androgen deprivation (AD) combined with high-dose three-dimensional conformal radiotherapy (3DCRT) for prostate cancer. Results of biochemical control are reported. PATIENTS AND METHODS: Between October 1999 and October 2001, 416 eligible patients with prostate cancer were assigned to one of three treatment groups according to their risk factors: 181 low-risk patients were treated with 3DCRT alone; 75 intermediate-risk patients were allocated to receive neoadjuvant AD (NAD) 4-6 months before and during 3DCRT; and 160 high-risk patients received NAD and adjuvant AD (AAD) 2 years after 3DCRT. Stratification was performed for treatment/risk group and total radiation dose. RESULTS: After a median follow-up of 36 months (range, 18 to 63 months), the actuarial biochemical disease-free survival (bDFS) at 5 years for all patients was 74%. The corresponding figures for low-risk, intermediate-risk, and high-risk disease were 80%, 73%, and 79%, respectively (P = .847). Univariate analysis showed that higher radiation dose was the only significant factor associated with bDFS for all patients (P = .0004). When stratified for treatment group, this benefit was evident for low-risk patients (P = .009) and, more interestingly, for high-risk patients treated with AAD. The 5-year bDFS for high-risk patients treated with AAD was 63% for radiation doses less than 72 Gy and 84% for those > or = 72 Gy (P = .003). CONCLUSION: The results of combined AAD plus high-dose 3DCRT are encouraging. To our knowledge, this is the first study showing an additional benefit of high-dose 3DCRT when combined with long-term AD for unfavorable disease.

Early stage infradiaphragmatic Hodgkin's disease: results of radiotherapy and review of the literature.

PURPOSE: To assess the impact of modality therapy on long-term outcome for infradiaphragmatic Hodgkin's disease (IDHD). METHODS AND MATERIALS: During the period 1965-1997, 847 patients with early stage Hodgkin's disease (HD) were evaluated and treated at our institution, 20 of them had IDHD (2.4%). Patients characteristics: stage I, nine patients (five pathological stage (PS), and four clinical stage (CS)) and stage II: 11 patients (six PS and five CS). Two modalities of treatment were used: combined modality (CMT), consisting of chemotherapy followed by extended field radiotherapy or radiotherapy alone (XRT). All patients with CS or PS II, except in one case, were treated with CMT. Overall, 12 patients were treated with CMT and the remaining eight patients were treated with XRT. RESULTS: The relapse rate after initial treatment was 30%. Ten-year disease free survival (DFS) and 10-year cause-specific survival were 60% and 92%, respectively. There was a non-significant trend to a better DFS for the CMT group of patients (76% vs. 35% for the whole series and 100% vs. 24% for stage I patients). The four relapsed patients in the XRT group were inguino-femoral PS I. In four out of the six patients who relapsed (66%) the failure was located solely in the supradiaphragmatic area, outside of the radiation fields. CONCLUSIONS: In our experience, inguino-femoral stage I patients have a high relapse rate after XRT; consequently, CMT consisting of chemotherapy plus involved field radiotherapy should be recommended for early stage HD confined below diaphragm.

New molecular targeted therapies integrated with radiation therapy in lung cancer.

Non-small-cell lung cancer (NSCLC) accounts for approximately 80%-85% of all cases of lung cancer; for patients with stage III disease, it accounts for approximately 40% of all cases. The treatment for unresectable stage III NSCLC is the combination of platinum-based chemotherapy and thoracic radiation. In this article, new targeted agents under investigation for possible integration into the combined therapy are reviewed. One of the most promising strategies is the inhibition of the epidermal growth factor receptor (EGFR) pathway. Radiation activates EGFR signaling, leading to radio-resistance by inducing cell proliferation and enhanced DNA repair. Several preclinical models have shown synergistic activity when cetuximab was combined with radiation therapy. Some phase II trials have evaluated the safety and efficacy of synchronous cetuximab and radiation therapy with promising results. Gefitinib has a radiosensitizing effect on cell lines and has been investigated in combination with radiation therapy for unresectable stage III NSCLC. However, disappointing results were observed in the maintenance treatment with gefitinib after chemoradiation therapy. Erlotinib has been tested in a phase I trial with chemoradiation therapy. Radiation induces tumor death by damaging cell membranes, DNA, and microvascular endothelial cells, which in response increase proangiogenic growth factors. Antiangiogenic agents reduce vascular density but improve tumor oxygenation. Use of vascular endothelial growth factor receptor (VEGFR) inhibitors enhances the therapeutic efficacy of irradiation in human NSCLC by hindering the repair of sublethal radiation damage. Trials combining erlotinib and bevacizumab with thoracic radiation are ongoing. New strategies must be developed for the integration of this triple-combination treatment. As radiation therapy enhances HSP90 chaperone function, causing radio-resistant lung cancer cells, therapeutic agents that block this path are likely candidates for decreasing radio-resistance by suppressing HIF-1alpha and VEGF expression and thus inhibiting the survival and angiogenic potential of lung cancer cells. Aurora kinase inhibitors with radiation therapy seem to have an additive effect in preclinical models in NSCLC and mesothelioma.

Linguistic adaptation and validation of the Spanish version of the Memorial Pain Assessment Card (MPAC).

INTRODUCTION: The Memorial Pain Assessment Card (MPAC), validated in 1987, is a card utilised for the self-assessment of cancer pain. The MPAC provides a quick, reliable measure of quality of life. MATERIALS AND METHODS: This study is a linguistic adaptation of the original version of the MPAC into the Spanish language and its validation. This was a multicentre, cross-sectional, observational study. Linguistic adaptation was carried out by four independent translators and two medical oncologists. The MPAC includes 4 subscales: three are visual analogue scales (VAS) measuring pain relief (VASPR), pain intensity (VASPI) and mood (VASMOOD). A fourth subscale consists of a set of pain severity descriptors (Tursky scale). RESULTS: VASPR has been validated in a subsequent prospective follow-up study. The validation of the MPAC subscales included: reliability (Cronbach's coefficient), internal validation (Spearman's coefficient) and external validation (McGill Pain Questionnaire, MPQ; Profile of Mood States, POMS; Hamilton Depression Scales, HDRS; and Zung Anxiety Scale, ZAS). A moderately high reliability of the VASPI, Tursky and VASMOOD subscales (alpha=0.72) was observed. Regarding internal validity, VASPI correlated significantly with Tursky and VASMOOD. However, they showed a non-significant correlation between each other. Regarding external validity, VASPI, Tursky and VASMOOD were correlated with most of the MPQ subscales. VASMOOD and Tursky correlated with most of the POMS subscales, but not with HDRS or ZAS. VASPI showed a non-significant correlation with all of the psychological distress measures. CONCLUSIONS: Our findings showed a successful validation of the VASPI, VASMOOD and Tursky subscales of the MPAC Spanish version.

El diapasón electrónico en la exploraciónde la audición / Electronic tuning fork in hearing examination

Al contrario que los Audiómetros, los Diapasones no han sido perfeccionados. Por ello hemos creado (un nuevo aparato), el Diapasón Electrónico, que siendo portátil y de bajo costo, nos permite una exploración mucho más completa. Tiene la forma de una pequeña caja rectangular y dispone de 6 frecuencias, de 128 a 4096 Hz, cada una con intensidades progresivas valoradas del 0 al 10. Con ella se conecta un Transductor o Vibrador, que explora la conducción aérea y la conducción ósea, en sus distintas modalidades, y valora los diferentes Tests auditivos. 300 exploraciones realizadas nos han demostrado su utilidad (AU)