Adjuvant radiochemotherapy for gastric cancer. Should we use prognostic factors to select patients?

Radiotherapy has a not well-established role in the pre-operative and in the post-operative setting in gastric cancer (GC) patients. Randomized trials report controversial outcomes and impact on survival. In the D2 loco-regional node resection era, after a well-performed radical surgery, local treatment using radiotherapy combined to chemotherapy should be considered for locally advanced GC. Prognostic factors could help the better selection of subgroups that present high risk of loco-regional recurrence. Then, the addition of radiotherapy could improve the disease-free survival and also quality of life. There are no large prospective studies that have assessed specific factors predicting for recurrence or survival, but only retrospective series, some of them including high number of patients with homogeneous characteristics. In locally advanced GC adding radiotherapy to the post-operative chemotherapy seems to improve outcomes and quality of life. Prognostic factors such as T-stage, N-status, nodal ratio, and other histological factors should be considered to submit patients to post-operative combined treatment. Larger prospective series are necessary to investigate the role of combined chemoradiation after radical D2-resection, especially in locally advanced GC. Further prospective investigations are needed to suggest prognostic factors that have significant impact on survival and recurrence, improving the management and outcomes, particularly in locally advanced GC patients

How technology can help in oncologic patient management during COVID-19 outbreak

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The role of stereotactic body radiation therapy in oligometastatic colorectal cancer

Rationale: Regorafenib is the new standard third-line therapy in metastatic colorectal cancer (mCRC). However, the reported 1-year overall survival rate does not exceed 25%. Patient concerns: A 55-year-old man affected by mCRC, treated with regorafenib combined with stereotactic body radiotherapy (SBRT), showing a durable response. Interventions: After 6 months of regorafenib, a PET/CT scan revealed a focal uptake in a solid lung nodule which was treated with SBRT, whereas continuing regorafenib administration. Fourteen months later, the patient had further progression in a parasternal lymph node, but treatment with regorafenib was continued. The regorafenib-associated side effects, such us the hand-foot syndrome, were favorable managed by reducing the dose from 160 to 120 mg/day. Outcomes: Patient-reported outcome was characterized by a progression-free survival of approximately 3 years. Lessons: in presence of oligometastatic progression, a local SBRT while retaining the same systemic therapy may be a better multidisciplinary approach. Moreover, disease progression is no longer an absolute contraindication for continuing the regorafenib treatment

Clinical Outcomes of Stereotactic Body Radiotherapy (SBRT) for Oligometastatic Patients with Lymph Node Metastases from Gynecological Cancers

Background: To evaluate clinical outcomes of stereotactic body radiation therapy (SBRT) as a local treatment for lymph node metastases from gynecological cancers. Methods: Between November 2007 and October 2021, we retrospectively analyzed 29 lymph node metastases in 22 oligometastatic/oligoprogressive patients treated with SBRT. The Kaplan-Meier method was used to estimate the rates survival. Univariate analysis for prognostic factors were performed with the log-rank test, and Cox proportional hazards regression was used to estimate hazard ratios (HR). Results: Median age was 62 years (IQR, 50-80 years). Median follow-up was 17 months (IQR 10.5-31 months). The median survival was 22 months (CI 95%: 4.2-39.7, IQR: 12.5-34.5 months). Six months, one year and two year overall survival (OS) were 96.6%, 85.2%, and 48.7%, respectively. Median local control (LC) was not reached. Six months, 1one year and 2 year were 93.1%, 87.9%, and 79.9%, respectively. Distant metastasis free survival (DMFS) at one year, and two year was 53% and 37.1%, respectively Four patients (18%) experienced acute G1-G2 toxicities. No G3-4 acute toxicity was reported, and no late toxicity was observed. Conclusions: SBRT for lymph node recurrence offers excellent in-field tumor control with safe profile and low toxicities. Size, number of oligometastases, and time primary tumor to RT seem to be significant prognostic factors

Fractionated stereotactic conformal radiotherapy for large benign skull base meningiomas

<p>Abstract</p> <p>Purpose</p> <p>to assess the safety and efficacy of fractionated stereotactic radiotherapy (FSRT) for large skull base meningiomas.</p> <p>Methods and Materials</p> <p>Fifty-two patients with large skull base meningiomas aged 34-74 years (median age 56 years) were treated with FSRT between June 2004 and August 2009. All patients received FSRT for residual or progressive meningiomas more than 4 centimeters in greatest dimension. The median GTV was 35.4 cm³(range 24.1-94.9 cm³), and the median PTV was 47.6 cm³(range 33.5-142.7 cm³). Treatment volumes were achieved with 5-8 noncoplanar beams shaped using a micromultileaf collimator (MLC). Treatment was delivered in 30 daily fractions over 6 weeks to a total dose of 50 Gy using 6 MV photons. Outcome was assessed prospectively.</p> <p>Results</p> <p>At a median follow-up of 42 months (range 9-72 months) the 3-year and 5-year progression-free survival (PFS) rates were 96% and 93%, respectively, and survival was 100%. Three patients required further debulking surgery for progressive disease. Hypopituitarism was the most commonly reported late complication, with a new hormone pituitary deficit occurring in 10 (19%) of patients. Clinically significant late neurological toxicity was observed in 3 (5.5%) patients consisting of worsening of pre-existing cranial deficits.</p> <p>Conclusion</p> <p>FSRT as a high-precision technique of localized RT is suitable for the treatment of large skull base meningiomas. The local control is comparable to that reported following conventional external beam RT. Longer follow-up is required to assess long term efficacy and toxicity, particularly in terms of potential reduction of treatment-related late toxicity.</p

Stereotactic Body Radiation Therapy Boost in Patients With Cervical Cancer Ineligible for Brachytherapy

Background: Standard treatment for locally advanced cervical cancer is external beam radiotherapy followed by brachytherapy (BT). Stereotactic body radiation therapy (SBRT) is a possible option for treating patients ineligible for BT. Patients and methods: From October 2012 to July 2020, nine women with cervical cancer received SBRT to high-risk volumes. The Kaplan-Meier method was used to estimate the rates of overall and disease-free survival. Results: The median age was 52 years; 88% of patients had squamous carcinoma. Reasons for forgoing BT were cervical canal stenosis, treatment refusal and hematological disease. The median boost dose was 18 Gy and the median dose per fraction was 6 Gy. Median follow-up was 16 months. The median survival was 24 months, the actuarial 2-year OS rate was 70%, and median disease-free survival was 11 months. One grade 3 late vaginal toxicity was reported. No acute nor late grade 4 toxicities were observed. Conclusion: SBRT boost in patients with cervical cancer ineligible for BT led to acceptable survival outcomes and a safe toxicity profile

Efficacy of residual site radiation therapy (ISRT) in patients with primary mediastinal lymphoma with Deauville Score 4 following R-CHT: results of a retrospective mono institutional study

Background: In order to evaluate the efficacy of residual site radiation therapy (RSRT) in terms of progression-free survival (PFS) and overall survival (OS) in patients with primary mediastinal lymphoma (PMBCL) with Deauville Score 4 (DS 4) following rituximab and chemotherapy treatment (R-ICHT). Methods: Thirty-one patients with PMBCL were recruited. After completion of R-ICHT, patients were staged with 18F-fluorodeoxyglucose positron-emission tomography, showing DS 4, and were treated with adjuvant RSRT. The chosen techniques for RT delivery were intensity-modulated radiation therapy (IMRT) or three-dimensional conformal RT (3D-CRT). Most patients underwent the first one using cone-beam computed tomography (CBCT). All patients were evaluated every 3 months for the first 2 years and every 6 months afterwards for a period of at least 5 years, with clinical and radiological procedures as required. Results: All patients received RSRT with a dose of 30 Gy in 15 fractions. The median follow-up time of 52.7 months (IQR: 26–64.1 months). The 5-year OS rate was 100%. The 2-year and 5-year PFS rates were 96.7% and 92.5%, respectively. Patients with relapsed disease had been treated with high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). Conclusion: RSRT in patients with PMBCL treated with ICHT and DS 4 did not impact unfavorably on patient survival

Stereotactic body radiation therapy for the treatment of lymph node metastases: a retrospective mono-institutional study in a large cohort of patients

IntroductionLymph node metastases (NMs) are a common site of tumor spread that can occur at different times of the disease. Stereotactic body radiation therapy (SBRT) can be a therapeutic option for the treatment of NMs in the setting of oligometastatic disease (OMD). The aim of this study was to evaluate as primary end points the local control (LC) and secondary end points the locoregional nodal control (LRNC), distant nodal control (DNC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS), and concurrently to assess the predictive factors of response.MethodsThis is a retrospective study that analyzes a group of patients treated with SBRT on NMs from different primary tumors, with a of maximum five metastasis. Treated lesions were divided into four groups: oligometastatics, oligorecurrents, oligoprogressives, and oligopersistents.ResultsFrom 2007 to 2021, 229 NMs were treated in 174 patients with different primary tumor. The schedule most represented was 30 Gy in five fractions. The LC was obtained in 90% of NMs treated by SBRT with rates at 1, 3, and 5 years of 93%, 86%, and 86%, respectively. The LRNC was reached in 84% of cases with rates at 1, 3, and 5 years of 88%, 83%, and 77%, respectively. The DNC was obtained in 87% of cases with rates at 1, 3, and 5 years of 92%, 82%, and 78%, respectively. The DMFS was obtained in 38% of cases with rates at 1, 3, and 5 years of 57%, 40%, and 30%, respectively. The rate of PFS were 44%, 23%, and 13% at 1, 3, and 5 years, respectively. The rates at 1, 3, and 5 years of OS were 78%, 48%, and 36%, respectively.ConclusionSBRT is an option for the treatment of NMS, with high rates of LC, improving survival, and with a good safety and tolerance. Tumor volume, tumor burden, lesion site, and doses can be predictive factors of response; however, multi-institutional studies with a greater number of patients could be helpful to better select patients and understand the right integrations between ablative treatment and systemic therapies

Residual Site Radiotherapy After Immunochemotherapy in Primary Mediastinal B-Cell Lymphoma: A Monoinstitutional Retrospective Study

Aim: To evaluate the efficacy of residual site radiation therapy (RSRT) on local control (LC), progressionfree (PFS) and overall (OS) survival in patients with primary mediastinal lymphoma (PMBCL), following rituximab and chemotherapy treatment (ICHT). Patients and Methods: The study included 34 patients with PMBCL treated between 2006 and 2014 with ICHT with/without autologous stem cell transplantation and RSRT. Between the end of ICHT/stem cell transplantation and RSRT, patients were evaluated with F-18-fluorodeoxyglucose positron-emission tomography. The gross tumor volume included morphological mediastinal residual disease after ICHT/SCT. The percentage of LC, PFS and OS were assessed. Results: All patients received RSRT with a median dose of 30 Gy. Median follow-up was 82 months. One patient out of 34 (3%) showed progressive disease 9 months from diagnosis. The 10-year PFS and OS were 97% and 97% respectively. Conclusion: RSRT in patients with PMBCL treated with ICHT did not impact unfavorably on LC and patient survival

Beyond BRCA1 and BRCA2: deleterious variants in DNA repair pathway genes in italian families with breast/ovarian and pancreatic cancers

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches