The role of different adjuvant therapies in locally advanced gastric adenocarcinoma

Complete surgical resection remains the only curative treatment option in locally advanced gastric cancer (GC). Several studies were conducted to prevent local recurrence and to increase the chance of cure. The aim of this study was to summarize our experience in locally advanced GC patients treated with adjuvant chemoradiotherapy (CRT) and to evaluate overall survival (OS), disease-free survival (DFS), toxicity rate and compliance to treatment

Successful role of adjuvant radiotherapy in a rare case of tracheal inflammatory myofibroblastic tumor: a case report

BACKGROUND:: Inflammatory myofibroblastic tumor (IMT) is a rare benign cancer that can express a more aggressive phenotype related to the genetic mutation of the anaplastic lymphoma kinase receptor (ALK). Involvement of trachea is extremely rare and due to the clinical and radiologic nonspecificity, the definitive diagnosis is based on the histologic evaluation of tissue specimens. Total surgical excision is curative and chemotherapy or radiotherapy has been employed in the treatment of unresectable tumors or as adjuvant therapies. CASE PRESENTATION:: The case described here is being reported because of the rare tracheal location and the atypical treatment approach used for an ALK-positive IMT. A 7-week pregnant woman voluntary interrupted pregnancy and underwent total surgical excision that resulted to have close margins. Although ALK-positive expression indicated the use of ALK inhibitors, she refused any type of adjuvant therapy that could affect ovarian function. Thus, 3D conformational external beam radiotherapy was performed with a daily dose of 180 cGy, 5 times per week, up to 45 Gy at the level of trachea. A total of 62 months of follow-up showed and no signs of disease recurrence or late radiation therapy-related toxicity. CONCLUSIONS: This report describes an extremely rare case of a tracheal IMT, underlying the key role of radiotherapy as adjuvant treatment able to definitively cure IMT, limiting systemic chemotherapy-related toxicity

Clinical benefit of adding oxaliplatin to standard neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a meta-analysis : Oxaliplatin in neoadjuvant treatment for rectal cancer

Abstract. Background: To evaluate the treatment tolerance and clinical outcomes in patients aged 70 years and older with locally advanced oropharyngeal cancer treated by definitive intensity-modulated radiation therapy (IMRT). Patients and Methods: We retrospectively analyzed 15 consecutive elderly patients, with histologically-proven squamous cell carcinoma of the oropharynx, staged T3-4 with or without involved lymph nodes at diagnosis, who received definitive sequential IMRT (70 Gy; 2 Gy/fraction). Adult Comorbidity Evaluation-27 (ACE-27) score was calculated and its influence on treatment tolerance and clinical outcomes was analyzed. Results: A total of 15 patients were included with a median age of 77 years (range=70-88 years). At baseline, 8 patients (53.3%) had an ACE-27 score of 1, and the remainder (n=7, 46.7%) had a comorbidity index of 0. All patients completed programmed IMRT treatment, without any reduction of total dose. Oral pain and mucositis were the most common acute side-effects, classified as grade 3 in 6 patients (40%) only. Xerostomia was reported in 13 patients (86.7%), without severe manifestation. There was no hematological toxicity. ACE-27 score was not related to higher severe acute toxicity. No patients experienced grade 3 or more late toxicity. Five-year overall survival and disease-free survival rates were 63.6% (95% confidence interval=32.7-83.3%) and 55% (95% confidence interval=24.4-77.6%), respectively. Comorbidity score did not influence survival outcomes, both overall survival (p=0.46) and disease-free survival (p=0.55). Conclusion: Treatment tolerance, as well as survival outcomes were good in elderly oropharyngeal cancer patients treated with definitive sequential IMRT. Due to age and comorbidity, no dose or volume reduction for IMRT should be considered in this setting of patients. A prospective randomized trial with a large sample size should be conducted to confirm our result

Clinical predictive factors of pathologic complete response in locally advanced rectal cancer

Background: Predictive factors of pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) are still not identified. The purpose of this study was to define them. Materials and Methods: Data from consecutive LARC patients treated between January 2008 and June 2014 at our Institution were included in the analysis. All patients were treated with a long course of nCRT. Demographics, initial diagnosis and tumor extension details, as well as treatment modalities characteristics were included in the univariate and logistic regression analysis. Results: In total 99 patients received nCRT, of whom 23 patients (23.2%) achieved pCR. Patients with and without pCR were similar in term of age, sex, comobidities, BMI and tumor characteristics. Multivariate logistic regression indicated that pre-treatment tumor size <= 5 cm was a significant predictor for pCR (p = 0.035), whereas clinical N stage only showed a positive trend (p = 0.084). Conclusions: Tumor size at diagnosis could be used to predict pCR, and thus to individualize therapy in LARC patients management. Validation in other studies is needed

Induction chemotherapy followed by neoadjuvant chemoradiotherapy and surgery in locally advanced rectal cancer: preliminary results of a phase II study

PURPOSE: To report preliminary results of induction chemotherapy (IC) followed by neoadjuvant chemoradiotherapy (CRT) and surgery in locally advanced rectal cancer (LARC) patients.MATERIALS AND METHODS: This is the preliminary evaluation of a phase II study. Patients with histologically proven rectal adenocarcinoma, stage II-III disease, who met the inclusion criteria, received induction FOLFOXIRI (5-FU, leucovorin, oxaliplatin and irinotecan) regimen in combination with targeted agents followed by CRT and surgery. Analysis of the first 8 patients was required to confirm the treatment feasibility before the accrual of 20 additional patients. RESULTS: The first 8 patients were evaluated. The median follow-up time was 23 months. There were no treatment-related deaths. Trimodality strategy was well tolerated with high compliance and a good level of toxicity. There were no evidence of febrile neutropenia and any grade 4 adverse events were recorded. Three patients had pathologic complete response (pCR) and 1 patient had a nearly pCR (ypT1 ypN0). CONCLUSION: Preliminary results are encouraging. FOLFOXIRI regimen plus targeted agents followed by CRT and surgery seems a safe approach. Longer follow-up and higher number of patients are mandatory to confirm such findings

High-resolution anoscopy predictive modeling of anal canal cancer response after definitive chemoradiotherapy in COVID19 era

Purpose: To develop a predictive index model, integrating both clinical and high-resolution anoscopy (HRA) features to further personalize the decision making process in anal canal carcinoma in COVID19 era.Methods and materials: We assess HRA parameters after definitive chemoradiotherapy in patients with anal canal malignant lesions.Results: HRA features could be important to assess the effect of CRT and a risk stratification system should be introduced in clinical practice to better allocate therapeutic interventions.Conclusion: To our knowledge this is the first proposal for HRA findings in anal canal cancer after definitive CRT. We believe that a risk score can be useful to estimate the risk of treatment failure (in term of persistence disease and/or recurrence) and its clinical relevance should not to be underestimated

Safety and efficacy of combining afatinib and whole-brain radiation therapy in treating brain metastases from EGFR-mutated NSCLC: a case report and literature review

Combining EGFR-tyrosine kinase inhibitors (TKIs) to whole brain radiation therapy (WBRT) has been shown to be more effective than EGFR-TKIs or WBRT alone in treating brain metastases (BMs) from EGFR-mutated Non Small-Cell Lung Cancer (NSCLC). However, despite the combination results well tolerated, EGFR-TKIs are often discontinued before WBRT, to reduce the risk of possible side effects, potentially resulting in reduced treatment efficacy and possible progression of intra- and extra-cranial disease. Afatinib, an irreversible inhibitor of EGFR-TK, has been shown to radiosensitize NSCLC in pre-clinical models and, compared to the other EGFR-TKIs, more efficiently penetrates the blood-brain barrier. However, nowadays, only two case reports describe the therapeutic efficiency and safety of combining afatinib with WBRT. Herein, we report on a 58-year-old woman patient with symptomatic BMs from NSLCL, treated with afatinib and concomitant WBRT, 30 Gy in 10 fractions. Treatment induced a remarkable and persistent radiological regression of BMs and the disappearance of neurological symptoms. However, the patient experienced severe skin toxicity of G3, corresponding to the irradiation area. Toxicity was successfully treated pharmacologically, and the patient did not experience any BMs-related symptoms for the next 10 months. She died of COVID-19-related respiratory failure. The association of afatinib with WBRT appears to be a successful strategy in the control of BMs from EGFR-mutated NSCLC. However, it should be considered that the combination could be responsible for serious dermatological toxicity

Cetuximab and Oral Mucositis: Is it Different from Oral Mucositis Caused by Other Drugs?

Purpose: To estimate frequency of oral mucositis in treatment for head and neck cancer with radiotherapy and concurrent cetuximab and to determine whether it has different characteristics from mucositis caused by other drugs. Materials and methods: Subjects with locally advanced, primary non-metastatic, squamous cell carcinoma located in the oropharynx were treated with radiation therapy plus concomitant cetuximab. Results: None of patients received their full planned course of combination treatment due to excessive mucosal toxicity. All patients developed oral mucositis within about 10-15 days: it began directly, without escalation, as grade ≥ 3; it was associated with severe pain and trismus; it was never associated to specific supra-infections; the evolution and the consequent resolution of clinical discomfort required several days and the treatment with corticosteroids did not represent the solution formula. Conclusion: Cetuximab induced oral mucositis have the following specific characteristics: time of onset, mode of clinical expression, severity, association with trismus and minimal response to corticosteroid therapy. Considering that the majority of studies do not reveal oral toxicity associated with cetuximab, future clinical trials should focus on specific topics to improve the definition of documented oral toxic effects

Reversibility of castration resistance status after Radium-223 dichloride treatment: Clinical evidence and Review of the literature

In the history of prostate cancer, some of patients progresses to castration resistant prostate cancer (CRPC) stage and, although new drugs and treatment protocols have been introduced, CRPC presents poor prognosis. This review focused on biological mechanisms, underlying CRPC described in scientific literature in order to explain the reversion of resistance to castration. We present the case of a 73 years-old man, affected by bone metastatic CRPC, early treated with Radium-223 with a complete response. After 15 months from Radium-223 treatment, PSA increased with radiological progression. ADT was again performed and was effective, despite previous CRPC condition and none known mechanisms that may explain the reversion of this condition. Therefore, to our knowledge, he is the unique described case of reversion of resistance to castration. Nevertheless, promising aspects may be lack of intrametastatic production of androgen or the suppression of bypass AR signaling pathways. Furthermore the cytotoxic action of Radium-223 on Cancer stem cell (CSC) , due to surrounding clones with high bone turnover, or the immune response that underlying the Abscopal effect, may also modulate the reversion of CRPC after Radium-223

Target volume delineation based on diffusion-weighted magnetic resonance imaging for locally advanced head and neck cancer

To compare gross tumor volume (GTV) definition in locally advanced head and neck squamous cell carcinoma (LAHNSCC) using diffusion-weighted magnetic resonance imaging (DW-MRI) and computed tomography (CT) with intravenous contrast