Intraoperative electron beam radiotherapy and perioperative high-dose-rate brachytherapy in previously irradiated oligorecurrent gynecological cancer: clinical outcome analysis

Background Pelvic recurrences from previously irradiated gynecological cancer lack solid evidence for recommendation on salvage. Methods A total of 58 patients were included in this clinical analysis. Salvage surgery was performed for locoregional relapse within previously irradiated pelvic area after initial surgery and adjuvant radiotherapy or radical external beam radiotherapy. The primary tumor diagnosis included cervical cancer (n = 47, 81%), uterine cancer (n = 4, 7%), and other types (n = 7, 12%). Thirty-three patients received adjuvant IOERT (1984–2000) at a median dose of 15 Gy (range 10–20 Gy) and 25 patients received adjuvant PHDRB (2001–2016) at a median dose of 32 Gy (range 24–40 Gy) in 6, 8, or 10 b.i.d. fractions. Results The median follow-up was 5.6 years (range 0.5–14.2 years). Twenty-nine (50.0%) patients had positive surgical margins. Grade ≥ 3 toxic events were recorded in 34 (58.6%) patients. The local control rate at 2 years was 51% and remained stable up to 14 years. Disease-free survival rates at 2, 5, and 10 years were 17.2, 15.5, and 15.5%, respectively. Overall survival rates at 2, 5, and 10 years were 58.1, 17.8, and 17.8%, respectively. Conclusions IOERT and PHDRB account for an effective salvage in oligorecurrent gynecological tumors. Patients with previous pelvic radiation suitable for salvage surgery and at risk of inadequate margins could benefit from adjuvant reirradiation in form of IOERT or PHDRB. However, the rate of severe grade ≥ 3 toxicity associated with the entire treatment program is relevant and needs to be closely counterbalanced against the expected therapeutic gain (AU)

Intraoperative electron beam radiotherapy and perioperative high-dose-rate brachytherapy in previously irradiated oligorecurrent gynecological cancer: clinical outcome analysis.

BACKGROUND: Pelvic recurrences from previously irradiated gynecological cancer lack solid evidence for recommendation on salvage. METHODS: A total of 58 patients were included in this clinical analysis. Salvage surgery was performed for locoregional relapse within previously irradiated pelvic area after initial surgery and adjuvant radiotherapy or radical external beam radiotherapy. The primary tumor diagnosis included cervical cancer (n = 47, 81%), uterine cancer (n = 4, 7%), and other types (n = 7, 12%). Thirty-three patients received adjuvant IOERT (1984-2000) at a median dose of 15 Gy (range 10-20 Gy) and 25 patients received adjuvant PHDRB (2001-2016) at a median dose of 32 Gy (range 24-40 Gy) in 6, 8, or 10 b.i.d. fractions. RESULTS: The median follow-up was 5.6 years (range 0.5-14.2 years). Twenty-nine (50.0%) patients had positive surgical margins. Grade ≥ 3 toxic events were recorded in 34 (58.6%) patients. The local control rate at 2 years was 51% and remained stable up to 14 years. Disease-free survival rates at 2, 5, and 10 years were 17.2, 15.5, and 15.5%, respectively. Overall survival rates at 2, 5, and 10 years were 58.1, 17.8, and 17.8%, respectively. CONCLUSIONS: IOERT and PHDRB account for an effective salvage in oligorecurrent gynecological tumors. Patients with previous pelvic radiation suitable for salvage surgery and at risk of inadequate margins could benefit from adjuvant reirradiation in form of IOERT or PHDRB. However, the rate of severe grade ≥ 3 toxicity associated with the entire treatment program is relevant and needs to be closely counterbalanced against the expected therapeutic gain.

Immune mechanisms mediating abscopal effects in radioimmunotherapy.

Radiotherapy of cancer has been traditionally considered as a local therapy without noticeable effects outside the irradiated fields. However, ionizing radiation exerts multiple biological effects on both malignant and stromal cells that account for a complex spectrum of mechanisms beyond simple termination of cancer cells. In the era of immunotherapy, interest in radiation-induced inflammation and cell death has considerably risen, since these mechanisms lead to profound changes in the systemic immune response against cancer antigens. Immunotherapies such as immunomodulatory monoclonal antibodies (anti-PD-1, anti-CTLA-4, anti-CD137, anti-OX40, anti-CD40, anti-TGFß), TLR-agonists, and adoptive T-cell therapy have been synergistically combined with radiotherapy in mouse models. Importantly, radiation and immunotherapy combinations do not only act against the irradiated tumor but also against distant non-irradiated metastases (abscopal effects). A series of clinical trials are exploring the beneficial effects of radioimmunotherapy combinations. The concepts of crosspriming of tumor neoantigens and immunogenic cell death are key elements underlying this combination efficacy. Proinflamatory changes in the vasculature of the irradiated lesions and in the cellular composition of the leukocyte infiltrates in the tumor microenvironment contribute to raise or dampen cancer immunogenicity. It should be stressed that not all effects of radiotherapy favor antitumor immunity as there are counterbalancing mechanisms such as TGFß, and VEGFs that inhibit the efficacy of the antitumor immune response, hence offering additional therapeutic targets to suppress. All in all, radiotherapy and immunotherapy are compatible and often synergistic approaches against cancer that jointly target irradiated and non-irradiated malignant lesions in the same patient.

Influence of different treatment techniques and clinical factors over the intrafraction variation on lung stereotactic body radiotherapy

Purpose: In the present study we compared three different Stereotactic body radiation therapy (SBRT) treatment delivery techniques in terms of treatment time (TT) and their relation with intrafraction variation (IFV). Besides that, we analyzed if different clinical factors could have an influence on IFV. Finally, we appreciated the soundness of our margins. Materials and methods: Forty-five patients undergoing SBRT for stage I lung cancer or lung metastases up to 5 cm were included in the study. All underwent 4DCT scan to create an internal target volume (ITV) and a 5 mm margin was added to establish the planning target volume (PTV). Cone-beam CTs (CBCTs) were acquired before and after each treatment to quantify the IFV. Three different treatment delivery techniques were employed: fixed fields (FF), dynamically collimated arcs (AA) or a combination of both (FA). We studied if TT was different among these modalities of SBRT and whether TT and IFV were correlated. Clinical data related to patients and tumors were recorded as potential influential factors over the IFV. Results: A total of 52 lesions and 147 fractions were analyzed. Mean IFV for x-, y- and z-axis were 1 ± 1.16 mm, 1.29 ± 1.38 mm and 1.17 ± 1.08 mm, respectively. Displacements were encompassed by the 5 mm margin in 96.1 % of fractions. TT was significantly longer in FF therapy (24.76 ± 5.4 min), when compared with AA (15.30 ± 3.68 min) or FA (17.79 ± 3.52 min) (p < 0.001). Unexpectedly, IFV did not change significantly between them (p = 0.471). Age (p = 0.003) and left vs. right location (p = 0.005) were related to 3D shift ≥2 mm. In the multivariate analysis only age showed a significant impact on the IFV (OR = 1.07, p = 0.007). Conclusions: The choice of AA, FF or FA does not impact on IFV although FF treatment takes significantly longer treatment time. Our immobilization device offers enough accuracy and the 5 mm margin may be considered acceptable as it accounts for more than 95 % of tumor shifts. Age is the only clinical factor that influenced IFV significantly in our analysis

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Stereotactic body radiotherapy (SBRT) for the treatment of inoperable stage I non-small cell lung cancer patients

Introduction: Lung cancer is the most frequent neoplasm in humans. Surgery is considered the best therapeutic approach for stage I non-small lung cell cancer (NSCLC). However, a remarkable amount of patients are considered as inoperable. Stereotactic body radiotherapy (SBRT) has risen as an option for those patients, rendering excellent results in quality of life and survival. Materials and methods: We analyzed clinical studies published between 2002 and 2015 which included SBRT as a treatment modality. Our own clinical series was analyzed as well. The patterns of failure following SBRT were investigated, together with the outcomes and the toxicity observed. Results: SBRT has proven to maintain an excellent local control. The analysis showed the tumor size and the histology as determinant factors for the response to treatment. Conclusion: According to the published evidence as well as our own experience, SBRT is a safe and feasible approach for early NSCLC. Its results may be comparable with surgery treatment (AU)

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Influence of different treatment techniques and clinical factors over the intrafraction variation on lung stereotactic body radiotherapy.

PURPOSE: In the present study we compared three different Stereotactic body radiation therapy (SBRT) treatment delivery techniques in terms of treatment time (TT) and their relation with intrafraction variation (IFV). Besides that, we analyzed if different clinical factors could have an influence on IFV. Finally, we appreciated the soundness of our margins. MATERIALS AND METHODS: Forty-five patients undergoing SBRT for stage I lung cancer or lung metastases up to 5 cm were included in the study. All underwent 4DCT scan to create an internal target volume (ITV) and a 5 mm margin was added to establish the planning target volume (PTV). Cone-beam CTs (CBCTs) were acquired before and after each treatment to quantify the IFV. Three different treatment delivery techniques were employed: fixed fields (FF), dynamically collimated arcs (AA) or a combination of both (FA). We studied if TT was different among these modalities of SBRT and whether TT and IFV were correlated. Clinical data related to patients and tumors were recorded as potential influential factors over the IFV. RESULTS: A total of 52 lesions and 147 fractions were analyzed. Mean IFV for x-, y- and z-axis were 1 ± 1.16 mm, 1.29 ± 1.38 mm and 1.17 ± 1.08 mm, respectively. Displacements were encompassed by the 5 mm margin in 96.1 % of fractions. TT was significantly longer in FF therapy (24.76 ± 5.4 min), when compared with AA (15.30 ± 3.68 min) or FA (17.79 ± 3.52 min) (p < 0.001). Unexpectedly, IFV did not change significantly between them (p = 0.471). Age (p = 0.003) and left vs. right location (p = 0.005) were related to 3D shift ≥2 mm. In the multivariate analysis only age showed a significant impact on the IFV (OR = 1.07, p = 0.007). CONCLUSIONS: The choice of AA, FF or FA does not impact on IFV although FF treatment takes significantly longer treatment time. Our immobilization device offers enough accuracy and the 5 mm margin may be considered acceptable as it accounts for more than 95 % of tumor shifts. Age is the only clinical factor that influenced IFV significantly in our analysis.

Stereotactic body radiotherapy (SBRT) for the treatment of inoperable stage I non-small cell lung cancer patients.

INTRODUCTION: Lung cancer is the most frequent neoplasm in humans. Surgery is considered the best therapeutic approach for stage I non-small lung cell cancer (NSCLC). However, a remarkable amount of patients are considered as inoperable. Stereotactic body radiotherapy (SBRT) has risen as an option for those patients, rendering excellent results in quality of life and survival. MATERIALS AND METHODS: We analyzed clinical studies published between 2002 and 2015 which included SBRT as a treatment modality. Our own clinical series was analyzed as well. The patterns of failure following SBRT were investigated, together with the outcomes and the toxicity observed. RESULTS: SBRT has proven to maintain an excellent local control. The analysis showed the tumor size and the histology as determinant factors for the response to treatment. CONCLUSION: According to the published evidence as well as our own experience, SBRT is a safe and feasible approach for early NSCLC. Its results may be comparable with surgery treatment.

Validación de técnicas de segmentación para la tomografía por emisión de positrones mediante imágenes ex-vivo de piezas quirúrgicas oncológicas / Validation of segmentation techniques for positron emission tomography using ex-vivo images of oncological surgical specimens

Objetivo: Diseñar una técnica novedosa de adquisición ex-vivo para establecer un marco común de validación de diferentes técnicas de segmentación para imágenes PET oncológicas. Evaluar sobre estas imágenes el funcionamiento de varios algoritmos de segmentación automática. Material y métodos: En 15 pacientes oncológicos se realizaron estudios PET ex-vivo de las piezas quirúrgicas extraídas durante la cirugía, previa inyección de 18F-FDG, adquiriéndose imágenes en 2 tomógrafos: un PET/CT clínico y un tomógrafo PET de alta resolución. Se determinó el volumen tumoral real en cada paciente, generándose una imagen de referencia para la segmentación de cada tumor. Las imágenes se segmentaron con 12 algoritmos automáticos y con un método estándar para PET (umbral relativo del 42%) y se evaluaron los resultados mediante parámetros cuantitativos. Resultados: La segmentación de imágenes PET de piezas quirúrgicas ha demostrado que para imágenes PET de alta resolución 8 de las 12 técnicas de segmentación evaluadas superan al método estándar del 42%. Sin embargo, ninguno de los algoritmos superó al método estándar en las imágenes procedentes del PET/CT clínico. Debido al gran interés de este conjunto de imágenes PET, todos los estudios se han publicado a través de Internet con el fin de servir de marco común de validación y comparación de diferentes técnicas de segmentación. Conclusiones: Se ha propuesto una técnica novedosa para validar técnicas de segmentación para imágenes PET oncológicas, adquiriéndose estudios ex-vivo de piezas quirúrgicas. Se ha demostrado la utilidad de este conjunto de imágenes PET mediante la evaluación de varios algoritmos automáticos (AU)

Objective: To design a novel ex-vivo acquisition technique to establish a common framework to validate different segmentation techniques for oncological PET images. To evaluate several automatic segmentation algorithms on this set of images. Material and methods: In 15 patients with cancer, ex-vivo PET studies of surgical specimens removed during surgery were performed after injection of 18F-FDG. Images were acquired in two scanners: a clinical PET/CT and a high-resolution PET scanner. Real tumor volume was determined in each patient, and a reference image was generated for segmentation of each tumor. Images were segmented with 12 automatic algorithms and with a standard method for PET (relative threshold at 42%) and results were evaluated by quantitative parameters. Results: It has been possible to demonstrate by segmentation of PET images of surgical specimens that on high resolution PET images, 8 out of 12 evaluated segmentation techniques outperformed the standard method, whose value is 42%. However, none of the algorithms outperformed the standard method when applied on images from the clinical PET/CT. Due to the great interest of this set of PET images, all studies have been published on the Internet in order to provide a common framework for validation and comparison of different segmentation techniques. Conclusions: We have proposed a novel technique to validate segmentation techniques for oncological PET images, acquiring ex-vivo PET studies of surgical specimens. We have demonstrated the usefulness of this set of PET images by evaluating several automatic segmentation algorithms (AU)

[Validation of segmentation techniques for positron emission tomography using ex-vivo images of oncological surgical specimens]. / Validación de técnicas de segmentación para la tomografía por emisión de positrones mediante imágenes ex-vivo de piezas quirúrgicas oncológicas.

OBJECTIVE: To design a novel ex-vivo acquisition technique to establish a common framework to validate different segmentation techniques for oncological PET images. To evaluate several automatic segmentation algorithms on this set of images. MATERIAL AND METHODS: In 15 patients with cancer, ex-vivo PET studies of surgical specimens removed during surgery were performed after injection of (18)F-FDG. Images were acquired in two scanners: a clinical PET/CT and a high-resolution PET scanner. Real tumor volume was determined in each patient, and a reference image was generated for segmentation of each tumor. Images were segmented with 12 automatic algorithms and with a standard method for PET (relative threshold at 42%) and results were evaluated by quantitative parameters. RESULTS: It has been possible to demonstrate by segmentation of PET images of surgical specimens that on high resolution PET images, 8 out of 12 evaluated segmentation techniques outperformed the standard method, whose value is 42%. However, none of the algorithms outperformed the standard method when applied on images from the clinical PET/CT. Due to the great interest of this set of PET images, all studies have been published on the Internet in order to provide a common framework for validation and comparison of different segmentation techniques. CONCLUSIONS: We have proposed a novel technique to validate segmentation techniques for oncological PET images, acquiring ex-vivo PET studies of surgical specimens. We have demonstrated the usefulness of this set of PET images by evaluating several automatic segmentation algorithms.

Intraoperative EBRT and resection for renal cell carcinoma : twenty-year outcomes.

PURPOSE: We report the outcomes of a multimodality treatment approach combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) with or without external beam radiation therapy (EBRT) in patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. PATIENTS AND METHODS: From 1983 to 2008, 25 patients with LR recurrent (n = 10) or LR advanced primary (n = 15) RCC were treated with this approach. Median patient age was 60 years (range, 16-79 years). Fifteen patients (60%) received perioperative EBRT (median dose, 44 Gy). Surgical resection was R0 (negative margins) in 6 patients (24%) and R1 (residual microscopic disease) in 19 patients (76%). The median dose of IOERT was 14 Gy (range, 9-15). Overall survival (OS) and relapse patterns were calculated using the Kaplan-Meier method. RESULTS: Median follow-up for surviving patients was 22.2 years (range, 3.6-26 years). OS and DFS at 5 and 10 years were 38% and 18% and 19% and 14%, respectively. LR control (tumor bed or regional lymph nodes) and distant metastases-free survival rates at 5 years were 80% and 22%, respectively. The death rate within 30 days of surgery and IOERT was 4% (n = 1). Six patients (24%) experienced acute or late toxicities of grade 3 or higher according to the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) v4. CONCLUSION: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach consisting of maximal surgical resection and IOERT with or without adjuvant EBRT yielded encouraging local control results, justifying further evaluation.

The multimodal management of locally advanced N2-non-small cell lung cancer: is there a role for surgical resection? A single institution's experience

BACKGROUND: The management of operable locally advanced N2 non-small cell lung cancer (NSCLC) is a controversial topic. Concurrent chemoradiation (CT-RT) is considered the standard of care for inoperable or unresectable patients, but the role of trimodality treatment remains controversial. We present our institution's experience with the management of stage III (N2) NSCLC patients, analyzing whether the addition of surgery improves survival when compared with definitive CT-RT alone. METHODS: From 1996 to 2006, 72 N2 NSCLC patients were treated. Thirty-four patients received cisplatin-based induction chemotherapy, followed by paclitaxel-cisplatin CT-RT, and 38 patients underwent surgery preceded by induction and/or followed by adjuvant therapy. Survival curves were estimated by Kaplan-Meier analysis, and the differences were assessed with the log-rank test. RESULTS: Most of the patients (87 %) were men. The median age was 59 years. A statistically significant association between T3-T4c and definitive CT-RT as well as between T1-T2c and surgery was noted (p < 0.0001). After a median follow-up period of 35 months, the median overall survival (OS) was 42 months for the surgery group versus 41 months for the CT-RT patients (p = 0.590). The median progression-free survival (PFS) was 14 months after surgery and 25 months after CT-RT (p = 0.933). Responders to radical CT-RT had a better OS than non-responders (43 vs. 17 months, respectively, p = 0.011). No significant differences were found in the OS or PFS between the pN0 [14 (37.8 %) patients] and non-pN0 patients at thoracotomy. Three treatment-related deaths (7.8 %) were observed in the surgical cohort and none in the CT-RT group. CONCLUSIONS: The addition of surgery did not render a median OS or PFS benefit when compared with CT-RT alone in our series of stage III-N2 NSCLC patients, in accordance with previously published data. However, responses to CT-RT had a greater impact in terms of OS and PFS. Although the patients selected for management including surgery showed a favorable T clinical staging in comparison to patients exclusively treated with definitive CT-RT, similar survival outcomes were found (AU)

Patterns of response after preoperative treatment in gastric cancer.

PURPOSE: To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution. METHODS AND MATERIALS: From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment. RESULTS: Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%. CONCLUSIONS: The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.

[Stereotactic radiation therapy]. / Radioterapia estereotáctica.

Stereotactic radiotherapy is a form of external radiotherapy that employs a system of three dimensional coordinates independent of the patient for the precise localisation of the lesion. It also has the characteristic that the radiation beams are conformed and precise, and converge on the lesion, making it possible to administer very high doses of radiotherapy without increasing the radiation to healthy adjacent organs or structures. When the procedure is carried out in one treatment session it is termed radiosurgery, and when administered over several sessions it is termed stereotactic radiotherapy. Special systems of fixing or immobilising the patient (guides or stereotactic frames) are required together with radiotherapy devices capable of generating conformed beams (lineal accelerator, gammaknife, cyberknife, tomotherapy, cyclotrons). Modern stereotactic radiotherapy employs intra-tumoural radio-opaque frames or CAT image systems included in the irradiation device, which make possible a precise localisation of mobile lesions in each treatment session. Besides, technological advances make it possible to coordinate the lesion's movements in breathing with the radiotherapy unit (gating and tracking) for maximum tightening of margins and excluding a greater volume of healthy tissue. Radiosurgery is mainly indicated in benign or malign cerebral lesions less than 3-4 centimetres (arteriovenous malformations, neurinomas, meningiomas, cerebral metastases) and stereotactic radiotherapy is basically administered in tumours of extracraneal localisation that require high conforming and precision, such as inoperable early lung cancer and hepatic metastasis.

Role of surgery in a multidisciplinary approach to superior sulcus tumors (SST): morbidity and prognostic factors for long-term success after resection.

BACKGROUND: Optimal management of SST is still controversial several years after the proposal of a multidisciplinary approach including neoadjuvant chemotherapy and external radiation. Our objective is to report our experience of this multidisciplinary approach from the surgical point of view. PATIENTS AND METHODS: From January 1997 to January 2008, 24 patients were treated surgically (18 with induction chemotherapy and 15 with radiotherapy). The surgical approach was thoracic (14 cases, 1 with a spinal approach) or cervical (10 patients, 2 thoracotomies). Pulmonary surgery performed consisted of 11 wedge resections, 10 lobectomies, 1 pneumonectomy and 2 cases without lung resection (1 exploratory thoracotomy and 1 local progression after a previously resected tumor). Intraoperative radiotherapy (IORT) was given in 7 cases. Partial vertebral body resection was performed in 5 cases. A pathologically complete response (pT0) was found in 7 cases (29 %). RESULTS: Surgery-related morbidity was mainly due to respiratory distress (5 patients). Two patients died in the first month after surgery (mortality: 8 %). The surgical approach (cervical vs. thoracic) did not influence postoperative morbidity ( p = NS). Overall 5-year survival was 56.6 % according to the Kaplan-Meier method. No influence on survival was observed with regard to the approach (cervical vs. thoracic), the use of IORT, or the performance of spinal surgery. Patients with a complete pathological response had a better 5-year survival, but this did not reach statistical significance. CONCLUSION: Surgery has a role in the multidisciplinary approach, especially when we consider long-term survival. A multidisciplinary approach using neoadjuvant chemo and radiotherapy has a high rate of complete pathological response. It is also associated with a high incidence of postoperative distress syndrome. The 5-year survival is acceptable.

Analysis of POSSUM score and postoperative morbidity in patients with rectal cancer undergoing surgery.

BACKGROUND: The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and later modifications (P-POSSUM y CR-POSSUM) have been used to predict morbidity and mortality rates among patients with rectal cancer undergoing surgery. These calculations need some adjustment, however. The aim of this study was to assess the applicability of POSSUM to a group of patients with rectal cancer undergoing surgery, analysing surgical morbidity by means of several variables. METHODS: between January 1995 and December 2004, 273 consecutive patients underwent surgery for rectal cancer. Information was gathered about the patients, tumour and therapy. To assess the prediction capacity of POSSUM, subgroups for analysis were created according to variables related to operative morbidity and mortality. RESULTS: The global morbidity rate was 23.6% (31.2% predicted by POSSUM). The mortality rate was 0.7% (6.64, 1.95 and 2.08 predicted by POSSUM, P-POSSUM and CR-POSSUM respectively). POSSUM predictions may be more accurate for patients younger than 51 years, older than 70 years, with low anaesthetic risk (ASA I/II), DUKES stage C and D, surgery duration of less than 180 minutes and for those receiving neoadjuvant therapy. CONCLUSION: POSSUM is a good instrument to make results between different institutions and publication comparable. We found prediction errors for some variables related to morbidity. Modifications of surgical variables and specifications for neoadjuvant therapy as well as physiological variables including life style may improve future prediction of surgical risk. More research is needed to identify further potential risk factors for surgical complications.

Predictive factors for radiation-induced pulmonary toxicity after three-dimensional conformal chemoradiation in locally advanced non-small-cell lung cancer.

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is a restricting complication of non-small-cell lung cancer irradiation. Three-dimensional conformal radiotherapy (3D-CRT) represents an advance because exposure of normal tissues is minimised. This study tries to identify prognostic factors associated with severe RP. MATERIALS AND METHODS: Eighty patients with stage IIIA (20%) and IIIB (80%) NSCLC treated with cisplatin- based induction chemotherapy followed by concurrent chemotherapy and hyperfractionated 3D-CRT (median dose: 72.4 Gy, range: 54.1-85.9) were retrospectively evaluated. Acute and late RP were scored using RTOG glossary. Potential predictive factors evaluated included clinical, therapeutic and dosimetric factors. The lungs were defined as a whole organ. Univariate and multivariate analyses were performed. RESULTS: Early and late RP grade>or=3 were observed in two patients (2%) and 10 patients (12%), respectively. Five patients (6%) died of pulmonary toxicity, 3 of whom had pre-existing chronic obstructive pulmonary disease (COPD). Median time to occurrence of late RP was 4.5 months (range: 3-8). Multivariate analysis showed that COPD (OR=10.1, p=0.01) and NTCPkwa>30% (OR=10.5, p=0.007) were independently associated with late grade>or=3 RP. Incidence of RP>or=3 grade for patients with COPD and/or NTCPkwa>30% was 25% vs. 4% for patients without COPD and NTCPkwa<30% (p=0.01). Risk of severe RP was higher for patients with COPD and/or NTCPkwa>30% (OR=7.3; CI 95%=1.4-37.3, p=0.016). CONCLUSIONS: COPD and NTCP are predictive of severe RP. Careful medical evaluation and meticulous treatment planning are of paramount importance to decrease the incidence of severe RP.

Radioterapia combinada con quimioterapia en el tratamiento del cáncer de pulmón / Radiotherapy for lung cancer. Integration with chemotherapy

El empleo conjunto de radioterapia y quimioterapia en el cáncer de pulmón no metastásico (microcítico y no microcítico) permite combinar los benefi cios de la radioterapia en términos de control local conaquellos conseguidos por la quimioterapia erradicando la enfermedad micrometastásica. Diversos estudios aleatorizados han demostrado que la radioterapia radical combinada con quimioterapia mejora la supervivenciade estos pacientes, a expensas de un incremento de la toxicidad. El desarrollo tecnológico y los avances en programas informáticos han posibilitado la introducción de nuevos aceleradores lineales comunicadoscon sofi sticados sistemas de planifi cación tridimensional que permiten administrar dosis mayores de irradiación al volumen tumoral diana y menores dosis de irradiación sobre estructuras sanas (pulmón, corazón,esófago y médula espinal). El resultado fi nal es un incremento del índice terapéutico debido a un probable benefi cio en el control local y una disminución de los efectos adversos de la irradiación. El volumen deirradiación, la dosis total a administrar, el fraccionamiento de la dosis, el tipo de esquema de combinación de la radioterapia con la quimioterapia,así como la infl uencia en la supervivencia de la irradiación cerebral profi láctica en el caso del cáncer microcítico de pulmón son temas de discusión en la actualidad

The combination of radiotherapy and chemotherapy in lung cancer (locally advanced non-small and small cell) may offer the benefi ts of radiotherapy in terms of local control and those of chemotherapy in terms of reducing metastatic dissemination of the disease. Severalrandomized studies have showed that radical radiotherapy combined with chemotherapy improves the survival of these patients at the expense of an increase in toxicity. The technological development and theimprovements in software have allowed the introduction of new linear accelerators and a three-dimensional planning system with the intention of delivering higher irradiation doses in the tumor target, and minimizingthe dose in adjacent normal tissues (lung, heart, esophagus and spinal cord). The volume of irradiation, the total dose, the fractionation, the schedule for the combination of radiotherapy and chemotherapy, as wellas the infl uence of the prophylactic cranial irradiation in small cell lung cancer are points for discussion at the moment

Predictive factors for radiation-induced pulmonary toxicity after three-dimensional conformal chemoradiation in locally advanced non-small-cell lung cancer

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) is a restricting complication of non-small-cell lung cancer irradiation. Three-dimensional conformal radiotherapy (3D-CRT) represents an advance because exposure of normal tissues is minimised. This study tries to identify prognostic factors associated with severe RP. MATERIALS AND METHODS: Eighty patients with stage IIIA (20%) and IIIB (80%) NSCLC treated with cisplatin- based induction chemotherapy followed by concurrent chemotherapy and hyperfractionated 3D-CRT (median dose: 72.4 Gy, range: 54.1-85.9) were retrospectively evaluated. Acute and late RP were scored using RTOG glossary. Potential predictive factors evaluated included clinical, therapeutic and dosimetric factors. The lungs were defined as a whole organ. Univariate and multivariate analyses were performed. RESULTS: Early and late RP grade>or=3 were observed in two patients (2%) and 10 patients (12%), respectively. Five patients (6%) died of pulmonary toxicity, 3 of whom had pre-existing chronic obstructive pulmonary disease (COPD). Median time to occurrence of late RP was 4.5 months (range: 3-8). Multivariate analysis showed that COPD (OR=10.1, p=0.01) and NTCPkwa>30% (OR=10.5, p=0.007) were independently associated with late grade>or=3 RP. Incidence of RP>or=3 grade for patients with COPD and/or NTCPkwa>30% was 25% vs. 4% for patients without COPD and NTCPkwa<30% (p=0.01). Risk of severe RP was higher for patients with COPD and/or NTCPkwa>30% (OR=7.3; CI 95%=1.4-37.3, p=0.016). CONCLUSIONS: COPD and NTCP are predictive of severe RP. Careful medical evaluation and meticulous treatment planning are of paramount importance to decrease the incidence of severe RP (AU)

Primary central nervous system lymphoma treated with rituximab plus temozolomide in a second line schedule.

We report a case of primary CNS lymphoma treated with high-dose methotrexate in the first line. After disease progression the patient received cranial radiotherapy with concomitant temozolomide, followed by rituximab plus temozolomide, with complete remission of the disease maintained for at least two years and without major toxicity.

Primary central nervous system lymphoma treated with rituximab plus temozolomide in a second line schedule

We report a case of primary CNS lymphoma treated with high-dose methotrexate in the first line. After disease progression the patient received cranial radiotherapy with concomitant temozolomide, followed by rituximab plus temozolomide, with complete remission of the disease maintained for at least two years and without major toxicity (AU)