Evaluation of Tumor Control and Normal Tissue Complication Probabilities in Patients Receiving Comprehensive Nodal Irradiation for Left-Sided Breast Cancer.

Women with left-sided breast cancer receiving adjuvant radiotherapy have increased incidence of cardiac mortality due to ischemic heart disease; to date, no threshold dose for late cardiac/pulmonary morbidity or mortality has been established. We investigated the likelihood of cardiac death and radiation pneumonitis in women with left-sided breast cancer who received comprehensive lymph node irradiation. The differences in dosimetric parameters between free-breathing (FB) and deep inspiration breath hold (DIBH) techniques were also addressed. Based on NTCP calculations, the probability of cardiac death was significantly reduced with the DIBH compared to the FB technique (p < 0.001). The risk of radiation pneumonitis was not clinically significant. There was no difference in coverage between FB and DIBH plans. Doses to healthy structures were significantly lower in DIBH plan than in FB plan for V20, V30, and ipsilateral total lung volume. Inspiratory gating reduces the dose absorbed by the heart without compromising the target range, thus reducing the likelihood of cardiac death.

Salvage radiotherapy in patients affected by oligorecurrent pelvic nodal prostate cancer.

PURPOSE: Metastasis-directed therapy (MDT) is an investigational treatment option in patients with oligorecurrent prostate cancer (PCa). The aim of this retrospective study is to report oncologic outcome and toxicity of elective nodal radiotherapy (ENRT) in PCa patients affected by pelvic nodal oligorecurrence. METHODS: 41 consecutive patients were treated with salvage radiotherapy. At biochemical recurrence after primary treatment, oligorecurrent disease was detected by positron emission tomography (PET) in 94% of the patients. Image-guided intensity modulated radiation therapy (IMRT) was delivered using tomotherapy. 83% of the patients received androgen deprivation therapy (ADT) in combination with ENRT. Survival analysis was performed with Kaplan-Meier method, log-rank test was used to analyze associations between survival end-points and clinical parameters. Multivariate analysis was performed using Cox proportional hazards regression models. Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. RESULTS: The median at follow-up was 33.6 months. At 3 years, overall survival (OS), cancer-specific survival (CSS), and biochemical progression-free survival (b-PFS) were 89%, 92%, and 53%, respectively. At univariate analysis, all survival end-points were correlated with the number of positive pelvic lymph nodes at oligorecurrence (≤ 3 vs > 3). Biochemical-PFS was correlated with PSA (p = 0.034) and PSA doubling time (p = 0.004) at oligorecurrence. At multivariate analysis, no independent variable was statistically significant. No patient experienced grade ≥ 2 late toxicity after radiotherapy. CONCLUSIONS: The number of metastatic lymph nodes and PSA doubling time seems to be important prognostic factors in the pelvic oligorecurrent setting. Salvage radiotherapy combined with short-course ADT might be a valid treatment strategy.

TLI in pediatric patients.

PURPOSE: Hematopoietic progenitor cell transplantation (HSCT) is a procedure used in different hematological diseases as part of the curative treatment, so the investigators propose a system of conditioning of reduced intensity based on total lymphoid irradiation (TLI) as an alternative to the classic total body irradiation (TBI) followed by haploidentical transplantation in patients compatible with a single HLA haplotype, as an alternative to patients who do not have an HLA compatible donor. MATERIALS AND METHODS: A cohort of 25 patients with hematological disease underwent haploidentical HSCT from February 2015 to May 2018, conditioned with TLI from day - 10 (2-4 days of treatment) followed by thiotepa (5 mg/kg/12 h) and melphalan (70 mg/m2/day) prior to HSCT and prophylaxis with ciclosporin (1.5 mg/kg/12 h). 2 Gy/fraction was administered to complete 8 Gy with IMRT and VMAT technique. RESULTS: 12% rejection of the transplant was obtained with acute GVHD < II (48%) and chronic GVHD 12%. No acute toxicity was recorded in irradiated patients and 56% survival of patients at the end of follow-up. CONCLUSION: Conditioning the haploidentical transplant with TLI, IMRT, and VMAT techniques compared with TBI and RT3D-C techniques is a feasible technique that helps inducing the necessary immunosuppression in patients with a high risk of graft rejection, minimal adverse effects, low incidence of GVHD, and high survival rate.

Added value of diffusion-weighted MRI for nodal radiotherapy planning in pelvic malignancies.

PURPOSE: To evaluate the added value of diffusion-weighted imaging (DWI) to T2-weighted imaging (T2WI) for improved identification of pelvic lymph nodes (LN) by radiation oncologists. METHODS/PATIENTS: This retrospective study included 20 patients with histopathologically proven node-negative prostate cancer. All patients underwent 3T-MRI of the prostate; matched axial T2WI and DWI sequences were assessed by an experienced uro-radiologist as the reference standard. Consultant and specialist registrar radiation oncologists were asked to identify all LN first on T2WI alone (read 1) and then on T2WI and DWI combined (read 2); LN were measured in size and divided into true positives (TP), false positives (FP) and false negatives (FN). Sensitivity, positive predictive value (PPV) and false negative rate (FNR) were then calculated and compared using Pearson's Chi square test. RESULTS: A total of 177 LN comprised the reference standard. 16 TP, 16 FP and 161 FN LN (sensitivity 9.0%, PPV 50.0%, FNR 91.0%) and 124, 15 and 53 LN (70.1%, 89.2%, 30%) were identified by reader 1 on reads 1 and 2, respectively; χ2 (2, N = 385) = 137.8, p < 0.0001. 27, 21 and 150 LN (15.3%, 56.3%, 84.8%) and 120, 13 and 57 LN (67.8%, 90.2%, 32.2%) were identified by reader 2 on the two reads; χ2 (2, N = 388) = 102.4, p < 0.0001. CONCLUSIONS: Adding DWI to T2WI significantly improved identification of pelvic LN by radiation oncologists and can therefore be regarded as a useful LN contouring technique for RT planning in pelvic malignancies.

Anal Cancer in the Era of Dose Painted Intensity Modulated Radiation Therapy: Implications for Regional Nodal Therapy.

Since the initial development of 5-fluorouracil and mitomycin as a standard of care platform for definitive anal cancer chemoradiotherapy, multiple studies have evaluated the optimal chemotherapy regimen, and radiotherapy technique. Refinements in treatment technique have taken place during an era of improved diagnostic imaging, including incorporation of FDG-PET, with implications for a possible stage migration effect. This has introduced an opportunity to develop stage-specific recommendations for primary tumor, involved nodal, and elective nodal irradiation dose. Elective nodal irradiation remains standard given the low rates of elective nodal failure with current practice, although may be subject to evolving controversy for patients with early stage disease. In this review, development of the current standard of care for anal cancer chemoradiotherapy is reviewed in the context of modern staging and dose-painted radiotherapy treatment techniques.

Impact of thoracic radiotherapy on respiratory function and exercise capacity in patients with breast cancer / Impacto da radioterapia torácica na função respiratória e capacidade de exercício em pacientes com câncer de mama

ABSTRACT Objective: To evaluate the impact of thoracic radiotherapy on respiratory function and exercise capacity in patients with breast cancer. Methods: Breast cancer patients in whom thoracic radiotherapy was indicated after surgical treatment and chemotherapy were submitted to HRCT, respiratory evaluation, and exercise capacity evaluation before radiotherapy and at three months after treatment completion. Respiratory muscle strength testing, measurement of chest wall mobility, and complete pulmonary function testing were performed for respiratory evaluation; cardiopulmonary exercise testing was performed to evaluate exercise capacity. The total radiotherapy dose was 50.4 Gy (1.8 Gy/fraction) to the breast or chest wall, including supraclavicular lymph nodes (SCLN) or not. Dose-volume histograms were calculated for each patient with special attention to the ipsilateral lung volume receiving 25 Gy (V25), in absolute and relative values, and mean lung dose. Results: The study comprised 37 patients. After radiotherapy, significant decreases were observed in respiratory muscle strength, chest wall mobility, exercise capacity, and pulmonary function test results (p < 0.05). DLCO was unchanged. HRCT showed changes related to radiotherapy in 87% of the patients, which was more evident in the patients submitted to SCLN irradiation. V25% significantly correlated with radiation pneumonitis. Conclusions: In our sample of patients with breast cancer, thoracic radiotherapy seemed to have caused significant losses in respiratory and exercise capacity, probably due to chest wall restriction; SCLN irradiation represented an additional risk factor for the development of radiation pneumonitis.

RESUMO Objetivo: Avaliar o impacto da radioterapia torácica na função respiratória e capacidade de exercício em pacientes com câncer de mama. Métodos: Pacientes com câncer de mama com indicação de radioterapia torácica após tratamento cirúrgico e quimioterápico foram submetidas a TCAR, avaliação respiratória e avaliação da capacidade de exercício antes da radioterapia torácica e três meses após o término do tratamento. Foram realizados teste de força muscular respiratória, medição da mobilidade torácica e prova de função pulmonar completa para a avaliação respiratória; realizou-se teste de exercício cardiopulmonar para avaliar a capacidade de exercício. A dose total de radioterapia foi de 50,4 Gy (1,8 Gy/fração) na mama ou na parede torácica, incluindo ou não a fossa supraclavicular (FSC). Histogramas dose-volume foram calculados para cada paciente com especial atenção para o volume pulmonar ipsilateral que recebeu 25 Gy (V25), em números absolutos e relativos, e a dose pulmonar média. Resultados: O estudo incluiu 37 pacientes. Após a radioterapia, observou-se diminuição significativa da força muscular respiratória, mobilidade torácica, capacidade de exercício e resultados da prova de função pulmonar (p < 0,05). A DLCO permaneceu inalterada. A TCAR mostrou alterações relacionadas à radioterapia em 87% das pacientes, o que foi mais evidente nas pacientes submetidas à irradiação da FSC. O V25% correlacionou-se significativamente com a pneumonite por radiação. Conclusões: Em nossa amostra de pacientes com câncer de mama, a radioterapia torácica parece ter causado perdas significativas na capacidade respiratória e de exercício, provavelmente por causa da restrição torácica; a irradiação da FSC representou um fator de risco adicional para o desenvolvimento de pneumonite por radiação.

Impact of thoracic radiotherapy on respiratory function and exercise capacity in patients with breast cancer.

OBJECTIVE: To evaluate the impact of thoracic radiotherapy on respiratory function and exercise capacity in patients with breast cancer. METHODS: Breast cancer patients in whom thoracic radiotherapy was indicated after surgical treatment and chemotherapy were submitted to HRCT, respiratory evaluation, and exercise capacity evaluation before radiotherapy and at three months after treatment completion. Respiratory muscle strength testing, measurement of chest wall mobility, and complete pulmonary function testing were performed for respiratory evaluation; cardiopulmonary exercise testing was performed to evaluate exercise capacity. The total radiotherapy dose was 50.4 Gy (1.8 Gy/fraction) to the breast or chest wall, including supraclavicular lymph nodes (SCLN) or not. Dose-volume histograms were calculated for each patient with special attention to the ipsilateral lung volume receiving 25 Gy (V25), in absolute and relative values, and mean lung dose. RESULTS: The study comprised 37 patients. After radiotherapy, significant decreases were observed in respiratory muscle strength, chest wall mobility, exercise capacity, and pulmonary function test results (p < 0.05). DLCO was unchanged. HRCT showed changes related to radiotherapy in 87% of the patients, which was more evident in the patients submitted to SCLN irradiation. V25% significantly correlated with radiation pneumonitis. CONCLUSIONS: In our sample of patients with breast cancer, thoracic radiotherapy seemed to have caused significant losses in respiratory and exercise capacity, probably due to chest wall restriction; SCLN irradiation represented an additional risk factor for the development of radiation pneumonitis.

Postoperative nodal irradiation in breast cancer patients with 1 to 3 axillary lymph nodes involved: the debate continues .

Regional lymph node irradiation is usually indicated in patients with positive node breast cancer. However, there are some controversies regarding the clinical benefits of adding regional nodal irradiation to whole-breast or thoracic-wall irradiation after breast surgery especially for patients with 1 to 3 positive axillary lymph nodes. More recently, two important studies (NCIC MA.20 and EORTC 22,922-10925) were published to address this significant issue and some further points need to be discussed.

Consensus on the regional lymph nodes irradiation in breast cancer.

Standard locoregional treatment of early-stage breast cancer currently consists of the conservative surgery and sentinel lymph node biopsy. In the event of positive sentinel node biopsy, an axillary level I-II lymphadenectomy should be carried out. However, recent publications have increasingly supported a tendency not to apply the surgical lymphadenectomy, but simultaneously, it has been developed a new role of regional radiotherapy, even if there is only 1-3 axillary lymph nodes involved. Given these new trends, radiation oncologists are facing the dilemma with regard to deciding about regional irradiation of breast cancer. For such purpose, The Spanish Group of Breast Cancer Radiation Oncology (GEORM as per its Spanish acronym) decided to reach a consensus to issue the respective guidelines for such types of cases. GEORM Managing Commission, gathering 13 members of different Spanish regional communities, issued a questionnaire including different clinical situations. These questions were set as key questions seeking responses, which were answered by 66 % out of the 75 members of the group. Following the response, the guidelines were drafted based on the replies to the mentioned questionnaire. All the respective issues were discussed by means of a virtual platform. In this article, we show the levels of consensus for different clinical situations, depending on the number of nodes involved and the type of surgical procedure performed on the axillary lymph nodes. The ongoing evolution of the oncological treatments obliges the radiation oncologists to take decisions without any existing clarifying evidence, and therefore, the consensus is necessary, which can assist in the decision-making process by the practitioners in such kinds of clinical situations.

Irradiación lumboaórtica en el cáncer cérvico uterino: análisis de la literatura / Radiotherapy of aortic-lumbar lymph nodes in the cervical cancer: literature review

Antecedentes: El cáncer de cuello uterino es una enfermedad prevalente en Chile y es una de las localizaciones tumorales más frecuentes tratadas en el Instituto Nacional del Cáncer. Es habitual recibir pacientes jóvenes con tumores avanzados, en etapas IIB y IIIB, con riesgo elevado de compromiso ganglionar, tanto pelviano como lumboaórtico y donde el tratamiento estándar es la radio-quimioterapia. Objetivos: Determinar si la irradiación lumboaórtica reduce el riesgo de recidiva y/o mejora la sobrevida en pacientes con compromiso ganglionar evidente y en aquellos con alto riesgo de compromiso a dicho nivel. Método: Revisión exhaustiva de la literatura publicada sobre la indicación de radioterapia lumboaórtica en el cáncer cérvico uterino, en pacientes con enfermedad evidente en los ganglios lumboaórticos y en aquellas en que la indicación es en casos de alto riesgo de compromiso en dicho nivel. Resultados: En pacientes con tumores cervicales de pequeño tamaño y con ganglios pelvianos positivos, sería beneficioso el tratamiento ganglionar lumboaórtico. Sin embargo, en aquellas pacientes con enfermedad pelviana masiva (IIIB)o en aquellas en que existe evidencia de enfermedad lumboaórtica, dicho beneficio no sería tan importante. Conclusión: Son las pacientes con enfermedad pelviana controlable y con elevado riesgo de tener compromiso ganglionar lumboaórtico (etapa IA-B, IIA-B con ganglios positivos en la pelvis), las que más se benefician de la radioterapia lumboaórtica.

Background: Uterine cancer is a prevalent disease in Chile and it is one of the most frequent cancer locations treated in the National Chilean Cancer Institute. It is also common to receive young patients that have advanced tumors in stages IIB and IIIB with high risks of compromises of lymphatic nodes of pelvis and aortic-lumbar zones. The treatment for these kinds of cancers is radio-chemotherapy. Aims: Determinate if the radiotherapy of aortic-lumbar lymph nodes lowers the chance of relapsing or increase the survival rate in patients with evident compromise of aortic-lumbar lymph nodes and in those with high risk of compromise in that level. Method: Exhaustive analysis of the literature about the indication of radiotherapy of aortic-lumbar lymph nodes in cervix cancer which is classified in those where the radiotherapy treatment is done in patients with evident compromise of aortic-lumbar lymph-nodes, and those where de radiotherapy is done in patients with high risk of compromise in that level. Results: In patients with small cervix tumors and positive lymphoid nodes the LA lymphatic nodes treatment would be beneficial. However, patients that suffer massive pelvic disease (IIIB) or that have evidence of the disease, the benefit would not be so important. Conclusion: Patients with controllable pelvic disease and with high risk of having aortic-lumbar lymph nodes compromise are the most benefit of radiotherapy in aortic-lumbar lymph nodes (stages IA-B, IIA-B with positive lymph nodes).

Preservation of ovarian function in young woman with hodgkin disease by laparoscopic medial transposition before abdominal irradiation.

A case of retro-uterine bilateral ovarian medial transposition in a 24-year-old women with Hodgkin's IIIB disease with bilateral compromised para-iliac ganglia is presented. A laparoscopic ovarian transposition toward a retro-uterine location out of the reach of the main radiation beam was made. The proximal pole of both ovaries was fixed to the ipsilateral uterosacral ligament. Two metallic clips were used to mark each distal ovarian pole to verify final position with x-rays. Preservation of the ovarian function was documented by hormonal levels 3 months after completing radiotherapy and regular yearly follow-up, until now. Normal menstruation patterns, similar to pretreatment history were recorded.

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.

Adjuvant radiotherapy in breast cancer--the treatment of lymph node areas.

Adjuvant radiotherapy decreases the risk of locoregional recurrences threefold, according to the results of many randomized trials and overviews. In patients treated with total mastectomy, the risk of local recurrence is mainly related to the number of involved axillary nodes, i.e. about 25%, 35% and 55% at 10 years when 1-3, 4-9 and 10 or more nodes are involved, respectively. In contrast, at 10 years, less than 15% of patients with negative axillary nodes relapse locally. The effect of adjuvant radiotherapy on distant metastases and overall survival is a controversial issue. On the one hand, recent results are compatible with the existence of a mechanism of secondary dissemination generated from locoregional tumor nests. The beneficial effect of radiotherapy can be observed whether with or without adjuvant systemic treatment. On the other hand, a deleterious late toxic effect, mainly cardiac, has also been shown. The importance of improvements in radiation techniques and quality assurance to obtain a positive balance in terms of overall survival is emphasized.

Endolymphatic irradiation in preparation for renal transplantation: a 26-year's follow-up.

OBJECTIVE: The aim of the present study was to analyze the long-term evolution of patients submitted to endolymphatic irradiation as a pre-transplant preparation. SETTING: Referral center of university hospital. DESIGN: Case-control study. MAIN OUTCOMES MEASURES: The study was designed to evaluate the incidence of rejection, kidney loss, leukopenia, infection, and graft survival in the group treated (group 1) prior to surgery, compared to a control group (group 2) composed of patients under identical clinical conditions (sex, age, type of donor, immunosuppressive therapy and time of transplant) that did not undergo treatment preparation. PATIENTS: Patients were selected from amongst transplantation candidates on a long-term waiting list, some with a high level of antibodies against panel. The control group was chosen from amongst recently transplanted patients. Patients in the treated group received lipoiodine containing 131I with specific activity ranging between 4 and 6 mCu/ml. RESULTS: A significant difference between the two groups was found with regard to the incidence of rejection crises (21.0% in group 1 and 73.6% in group 2; P = 0.003), and the maintenance dose of azathioprine (smaller in group 1; P < 0.01). As to kidney graft loss due to rejection, a tendency to significance could be identified (10.5% in group 1 and 42.1% in group 2; P = 0.063); however, the difference was not significant between the two groups in terms of reversibility of rejection episodes during the first 60 post-transplant days. CONCLUSIONS: The authors concluded that this method, besides being relatively innocuous (there was no compromising of either the thyroid gland or of gonad function and there was no increase in tumor incidence), has an extended immunosuppressive effect, and can be indicated for cadaveric renal allograft recipients, especially those showing high panel reactivity.

[Treatment of the regional lymph nodes in squamous carcinoma of the penis]. / Tratamiento de los ganglios regionales en el carcinoma escamoso de pene.

OBJECTIVES: We evaluated the management of the regional lymph nodes to determine the appropriate treatment for carcinoma of the penis. METHODS: The records of 36 patients with carcinoma of the penis were reviewed. Lymphadenectomy was performed in 18 patients, 17 were managed conservatively (watchful waiting) and 1 patient had a biopsy and received radiotherapy. RESULTS: Positive nodes were found in 2 of 2 pT4, 2 of 3 pT3, 8 of 13 pT2 and 2 of 12 pT1 patients submitted to lymphadenectomy. Concerning the histological grade, positive nodes were found in all of the 4 G3, 5 of 12 G2 and 3 of 20 G1 patients. The survival rate was 100% for the patients with negative lymph nodes (pNO = 6) or a single positive inguinal lymph node (pN1 = 5). A correlation was found between the T and the histological grade and the likelihood of lymph node invasion. CONCLUSIONS: The T and the histological grade of the primary lesion must be considered when deciding the approach in the management of the lymph nodes as unnecessary lymphadenectomy can be avoided and those at high risk of lymph node invasion can be treated radically and timely.

Modified clearing technique to identify lymph node metastases in post-irradiated surgical specimens from rectal adenocarcinoma

The aim of this study is to describe a modification of the original method of clearing lymph nodes in specimens from rectal adenocarcinoma and its yield in comparison to a control group whose specimens were studied by a manual technique. There were 32 consecutive patients with locally advanced rectal adenocarcinoma. All patients received preoperative radiation therapy (PRT) at doses of 45 Gy, concomitant with 5-fluourouracil at the doses of 450 mg/m² IV bolus, days 1-5 and 28-33 of PRT; 4-8 weeks later radical surgery with a curative intent was performed. Twenty two specimens were studied by a manual technique consisting of fixation in 10 per cent formalin. Ten specimens wer studied with the modified clearing technique consisting of administration through the inferior mesenteric artery of methylene blue; fixation with 10 per cent formalin plus 0.01 per cent of methylene blue; clearing the fat with a sequence of 95 per cent alcohol - 100 per cent acetone - 100 per cent xylene. In the 32 specimens, 413 lymph nodes were found. Using the manual technique 104 lymph nodes were found (average 4.7 lymph nodes per specimen); 309 lymph nodes by the modified clearing technique (average 30.9 lymph nodes per specimen), (p<0.0001). Using the manual technique 23 out of 104 lymph nodes (22 per cent) contained metastases. All metastatic lymph nodes measered > 5 mm; 18 out of 23 metastatic lymph nodes were located on the perirectal area (level 2); and five were located in the root of the inferior mesenteric artery (level 5). Using the modified clearing technique is a quick, easy and reproducible method for identifying lymph nodes in post-irradiated surgical specimens. In comparison to the traditional manual method of searching for lymph nodes, it improves in the detection of small lymph nodes (>5 mm), allowing better staging in patients with rectal adenocarcinoma