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.

Definitive weekly hypofractionated radiotherapy in cutaneous squamous cell carcinoma: response rates and outcomes in elderly patients unfit for surgery.

INTRODUCTION: The optimal definitive radiotherapy (RT) scheme in cutaneous squamous cell carcinoma (cSCC) remains controversial, especially in elderly patients. METHODS: Data of elderly patients with cSCC lesion(s) treated with weekly hypofractionated RT (8 Gy per week per 7-8 weeks) were analyzed. RESULTS: Eighteen patients (median age 89 years) with 23 cSCC lesions have been identified including nine males (50%) and nine females (50%). The most common tumor localization was the head and neck region (n = 21; 91.3%), and the majority of lesions (n = 15; 65.2%) was stage ≥ III. At diagnosis, pain and bleeding were ascribed in 13 (56.5%) and eight (34.8%) cSCC, respectively. Compliance with weekly hypofractionated RT was excellent. The overall response rate at 12 weeks after treatment was 95.7%. Bleeding and pain relief were achieved in all cases. Severe toxicity was not recorded. The 1-year overall survival was 66.0%. The 1-year progression-free survival was 58.7%. CONCLUSIONS: Weekly hypofractionated RT provides a safe, efficient, and cost-effective treatment in elderly cSCC patients with minimal side effects.

Treatment in locally advanced rectal cancer: a machine learning bibliometric analysis.

A bibliometric analysis was performed using a machine learning bibliometric methodology in order to evaluate the research trends in locally advanced rectal cancer treatment between 2000 and 2020. Information regarding publication outputs, countries, institutions, journals, keywords, funding, and citation counts was retrieved from Scopus database. During the search process, a total of 2370 publications were identified. The vast majority of papers originated from the United States of America, reflecting also its research drive in the collaboration network. Neoadjuvant treatment was the topic most studied in the highly cited studies. New keywords, including neoadjuvant chemotherapy, multiparametric magnetic resonance imaging, circulating tumor DNA, and genetic heterogeneity, appeared in the last 2 years. The quantity of publications on locally advanced rectal cancer treatment since 2000 showed an evolving research field. The 'new' keywords explain where research is presently heading.

The INCH Trial - Induction Chemotherapy in Patients With Bulky Anal Canal Cancer: Evaluation of the Pilot Phase.

AIM: To assess feasibility, complications and efficacy of induction chemotherapy followed by standard chemoradiotherapy in patients with bulky anal canal cancer. PATIENTS AND METHODS: Patients with squamous cell carcinoma of the anal canal, staged bulky tumor with or without nodal involvement were prospectively enrolled. Before standard chemoradiotherapy, patients received induction chemotherapy with 3 cycles of 75 mg/m2 cisplatin and 750 mg/m2 5-fluorouracil. Patients were followed-up routinely until recurrence or death. RESULTS: Seven patients with bulky anal canal cancer were evaluable for this pilot phase of the study. All patients had human papillomavirus-negative disease. Five completed the scheduled induction chemotherapy and all patients completed the programmed concomitant chemoradiotherapy. None had severe hematological toxicity. The majority of patients (6/7) had tumor downsizing after induction treatment. Six months after chemoradiotherapy, complete response was documented in three patients and salvage surgery was performed in two cases. With a median follow-up of 38 months (range=28-48 months), two patients are disease-free survivors. CONCLUSION: Induction chemotherapy has the potential to become a standard approach in patients with bulky human papillomavirus-negative anal canal cancer.

Functional lung volume mapping with perfusion Single-Photon Emission Computed Tomography scan for radiotherapy planning in patients with locally advanced nonsmall cell lung cancer.

OBJECTIVES: Radical chemotherapy-radiotherapy represents the standard treatment for locally-advanced nonsmall cell lung cancer (NSCLC). Conventional radiotherapy achieves limited local tumor control, but dose escalation to the primary tumor is prevented by radiotherapy-induced toxicity. The aim of this study was to evaluate feasibility of tailored intensity-modulated radiotherapy (IMRT) planning based on lung single-photon emission computed tomography (SPECT) perfusion data and to compare functional and conventional dose-volume parameters. METHODS: A total of 21 patients were prospectively enrolled. Patients underwent IMRT treatment with 2 Gy/fraction (median total dose of 60 Gy). Lung perfusion SPECT images were acquired before radiotherapy and 3 and 6 months after radiotherapy completion. SPECT and planning computed tomography images were co-registered using MIM-MAESTRO software with 3D-PET Edge algorithm. Lung volumes were defined anatomically as total lung and functionally as total not functional lung and total functional lung. Dose-volume histograms were calculated using QUANTEC constraints [mean lung dose (MLD)<20 Gy, V20<20%]. For each patient, conventional and functional radiotherapy plans were generated and compared. RESULTS: A total of 19 of 21 patients with NSCLC were included (mean age 66 years, 11 stage IIIA, 8 stage IIIB), 12/19 patients completed the 6-months follow-up. A significant reduction of mean V20 was observed in functional radiotherapy planning compared to conventional plan (405.9 cc, P < 0.001). Mean MLD was also lower in the SPECT-based plans, but the difference was not statistically relevant (0.8 Gy, P = 0.299). G2 radiation pneumonitis was observed in two patients. CONCLUSIONS: Functional radiotherapy planning allowed to decrease functional lung irradiation compared to conventional planning. The possibility to limit radiotherapy-induced toxicity could allow us to perform an effective dose-escalation to target volume.

Impact of clinical complete response on treatment outcomes in patients with locally advanced HPV-negative oropharyngeal squamous cell carcinoma.

OBJECTIVE: To evaluate treatment outcomes after definitive chemoradiotherapy (CRT) for human papilloma virus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: We analyzed data concerning HPV-negative OPSCC patients treated with curative intent. All patients received concomitant high-dose cisplatin-based chemotherapy. Two different RT techniques were used: (1) sequential boost IMRT (S-IMRT) to a total dose of 70 Gy (2 Gy/fraction); (2) simultaneously integrated boost (SIB-IMRT) to a total dose of 67.5 Gy (2.25 Gy/fraction). Survival outcomes were estimated. RESULTS: In total, 69 HPV-negative OPSCC patients were included (n = 40 S-IMRT; n = 29 SIB-IMRT). The median follow-up time was 40 months. The 3-year overall survival, disease-free survival, distant metastasis-free survival and locoregional-free survival were 67.1%, 63.3%, 64.5% and 66.0%, respectively. Alcohol abuse and advanced stage disease at presentation were the main risk factors for worse survival outcomes. Complete clinical response (cCR) at 3 months after CRT improved overall survival (86.3% versus 42.5%, p < 0.01). The cCR events were greater but not statistically significant in SIB-IMRT group compared to S-IMRT patients (69% versus 47.5%, p = 0.09). CONCLUSIONS: The positive impact of cCR at 3 months on survival needs to be confirmed in randomized clinical trials, as well as its close correlation with SIB-IMRT technique. A proper stratification of HPV-negative OPSCC patients should be paramount to tailor treatment strategy in the near future.

Tolerability of Oxaliplatin-based Neoadjuvant Chemoradiotherapy in Elderly Locally Advanced Rectal Cancer Patients: A Case-control Study of a Real-life Experience.

BACKGROUND/AIM: The aim of this study was to delineate clinical criteria to safely select elderly patients who can benefit from adding oxaliplatin to 5-fluoruracil-based neo-adjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) management. PATIENTS AND METHODS: This is a single-institutional case-control study on LARC patients who received intensified neo-adjuvant CRT, between January 2007 and December 2014. Data concerning patient characteristics, treatment details and adverse events were reviewed and analyzed in two settings: young patients (<65 years) and elderly (≥65 years). A binary logistic model was applied to analyze the potential interaction between clinical variables and severe toxicity risk. RESULTS: In total, 100 consecutive LARC patients were included. Mean age was 63.6 years and 55% (n=55) of the patients had adult comorbidity evaluation-27 (ACE-27) score ≥1. Most cancers (81%) were lymph node positive at diagnosis. Overall, ≥5 cycles of oxaliplatin were administered to 92 patients (92%). Only 17 patients (17%) reported grade ≥3 toxicity. The elderly group did not experience significantly higher severe toxicity than the young group. ACE-27 score ≥1 was the only variable independently associated with a higher severe toxicity. The 5-year overal survival (OS) rates were 64.1% and 89.2% in the elderly and young cohort, respectively. CONCLUSION: Elderly LARC patients can be safely treated with intensified neo-adjuvant CRT.

Successful Treatment of Anal Canal Cancer Metastasis to the Cranial Bones: A Case Report and Literature Review.

Single metastasis to the cranial bone represents a very uncommon occurrence that can arise from an anal canal cancer. No cases of cranial bone metastasis from anal canal carcinoma are available in the literature. Herein, we present a case of a unique metastatic lesion to the right parietal bone that occurred after curative chemoradiotherapy of primary squamous cell anal canal carcinoma. The patient received radiotherapy and systemic platinum-based chemotherapy, with optimal local control, high compliance and a well tolerable level of toxicity.

Hypofractionated radiotherapy combined with cetuximab in vulnerable elderly patients with locally advanced head and neck squamous cell carcinoma.

This study was designed to evaluate the objective response after hypofractionated radiotherapy (HFRT) combined with cetuximab (HFBRT) in vulnerable elderly patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Vulnerable elderly patients with histologically proven HNSCC received HFRT (total dose 60 Gy, 3 Gy/fraction) with concurrent cetuximab (250 mg/m2 with a loading dose of 400 mg/m2 1 week before HFRT). Elderly patients were categorized as vulnerable based on mini-cog test and adult comorbidity evaluation-27 score. All patients completed the programmed HFRT and two patients received the planned cetuximab infusion. Severe acute toxicity, observed in four patients, was gastrointestinal (oral mucositis in four cases; nausea/vomiting in one case) and dermatological (acneiform eruption in three cases; radiation dermatitis in one case). Three serious adverse events were recorded in three out of six patients Overall, three patients had a partial response and three patients had progression disease 3 months after the end of the treatment. No complete response was observed. HFBRT seems to be not a safer alternative approach for vulnerable elderly patients with locally advanced HNSCC. Further prospective trials are needed to define better tumor control with less incidence of toxic effects in vulnerable elderly HNSCC patients.

Hypofractionated intensity-modulated radiotherapy in locally advanced unresectable pancreatic cancer: A pilot study.

PURPOSE: To test feasibility and safety of hypofractionated intensity modulated radiotherapy (H-IMRT) in pancreatic adenocarcinoma (PAC) treatment. METHODS: Patients with unresectable nonmetastatic PAC were prospectively enrolled on a pilot study. Patients received H-IMRT to gross tumor volume to a total dose of 52 Gy (4 Gy/fraction). Toxicity rates, duodenal dosimetric parameters, and clinical outcomes were evaluated. RESULTS: Ten patients received H-IMRT regimen. Objective tumor response was recorded in all patients but one. Gastrointestinal toxicity was the most common acute side effect and its severity moderately correlated with duodenal maximum dose (ρ = 0.46) and percentage of duodenal volume exposed to 5 Gy (ρ = 0.46). The 1-year overall and disease-free survival were 83.3% and 68.6%, respectively. CONCLUSION: H-IMRT seems to guarantee a high local control rate without severe toxicity. Its use in unresectable nonmetastatic PAC needs to be further investigated.

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.

Prognostic significance of inflammatory-related parameters in patients with anal canal cancer.

PURPOSE: To investigate the correlation between inflammatory-related parameters and overall survival (OS) and disease-free survival (DFS) in anal canal cancer population. METHODS AND MATERIALS: Patients diagnosed with anal canal carcinoma and treated with curative intent chemoradiotherapy (CRT) were included. Data about pre-treatment complete blood count were collected. Neutrophil to lymphocyte ratio (NLR), fibrinogen (F), and a combination of these (F-NLR score) were correlated with OS. RESULTS: A total of 58 patients were enrolled. In multivariate analysis, the strongest OS prognostic factor was NLR, with a hazard ratio (HR) for low NLR compared to high NLR of 1.30 (95% confidence interval 1.01-14.12). Kaplan-Meier survival analysis showed that patients with high NLR, F, and F-NLR had significantly shorter OS and DFS. CONCLUSION: To our knowledge, this is the first study providing evidence that elevated pre-treatment NLR, F, and F-NLR score significantly correlate with worse survival outcomes in patients with anal canal carcinoma. In view of our findings, future clinical trials in anal canal cancer patients are warranted to verify our results.

Prognostic Significance of the Neutrophil/Lymphocyte Ratio in Patients with Non-Human Papilloma Virus-Related Oropharyngeal Cancer: A Retrospective Cohort Study.

PURPOSE: To investigate the effects of the pretreatment neutrophil-to-lymphocyte ratio (N/L) on non-human papilloma virus (HPV)-related oropharyngeal cancer. MATERIALS AND METHODS: N/L was calculated by dividing the neutrophil count by the lymphocyte count. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of N/L and other clinical factors on survival outcomes. High/low N/L groups were defined as > 4.7 and ≤4.7, respectively. RESULTS: Data of 57 consecutive patients with non-HPV-related oropharyngeal cancer were analyzed. The 3-year disease-free survival was 79 versus 36.9% in favor of the low N/L group (p = 0.04). The 5-year overall survival was 71.6 versus 53.3% in the low N/L and high N/L group, respectively (p = 0.07). CONCLUSION: N/L could play an important role in non-HPV-related oropharyngeal cancer progression and indicate prognosis.

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 the patients progressed to castration-resistant prostate cancer (CRPC) stage and, although new drugs and treatment protocols have been introduced, CRPC presents poor prognosis. This review is 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-year-old man, affected by bone metastatic CRPC, early treated with Radium-223 with a complete response. After 15 months from Radium-223 treatment, prostate-specific antigen increased with radiological progression. Androgen deprivation therapy was again performed and was effective, despite previous CRPC condition and no known mechanisms that may explain the reversion of this condition. Therefore, to our knowledge, he is the unique described case of the reversion of resistance to castration. Nevertheless, promising aspects may be lack of intrametastatic production of androgen or the suppression of bypass androgen receptor 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. If confirmed by multicenter trials, the reversion of CRPC may impact on the management of prostate cancer.

The role of different adjuvant therapies in locally advanced gastric adenocarcinoma.

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: Locally advanced GC stage IB-III were included. Adjuvant CRT consisted of 45-50.4 Gy (1.8 Gy/day, 5 days/week) with concomitant Macdonald regimen (Mcd) or Epirubicin, Cisplatin and 5-Fluorouracil (ECF) scheme. Univariate and multivariate analysis of several prognostic factors for OS was conducted. RESULTS: Fourty-nine GC patients were treated: 24 received Mcd and 25 received ECF. Median follow up was 48 months. Acute grade 3-4 toxicity was observed in 6 patients. The 2-year and 5-year OS rates were 65.3% and 41.5%, respectively. The 2-year and 5-year DFS were 59.2% and 41.2%, respectively. No prognostic factors were significantly associated with OS. CONCLUSIONS: Adjuvant CRT is a feasible strategy in locally advanced GC. It has an acceptable toxicity rate and it is able to increase both DFS and OS.

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

BACKGROUND AND 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.

Definitive Chemoradiotherapy for Anal Carcinoma: Long-Term Results Based on Consistent Time-to-Event Endpoints.

AIM: To report the long-term results after definitive chemoradiotherapy (CRT) for anal carcinoma, using consistent time-to-event endpoints. METHODS AND MATERIALS: Anal carcinoma patient charts were reviewed. All patients received definitive CRT. Overall survival (OS), local failure-free survival (LFFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and anal dysfunction-free survival (ADFS) were estimated. RESULTS: In total, 65 patients were included. CRT was well tolerated, with only 24.6% grade ≥3 acute toxicity. Overall, the 5-year OS, LFFS, LRFFS, and DMFS were 75.3, 60.2, 74.2, and 66.2%, respectively. Early complete clinical response and tumor stage at diagnosis were the strongest predictors of OS (p = 0.04) and local failure (p = 0.03), respectively. CONCLUSIONS: In the treatment of anal cancers, excellent ADFS and OS, and valid LFFS, LRFFS, and DMFS can be achieved with definitive CRT. Adequacy of time-to-event endpoints is paramount.

Intensified Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer in Elderly Patients: Toxicity, Disease Control, and Survival Outcomes.

INTRODUCTION: We report the treatment compliance, toxicity rates, and long-term clinical outcomes of elderly patients who received intensified neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We identified a retrospective cohort of patients aged ≥ 70 years with LARC who received intensified neoadjuvant CRT, followed by surgery and adjuvant chemotherapy, from 2007 to 2014. Intensified neoadjuvant CRT consisted of radiotherapy (total dose, 50.4/54 Gy) with concomitant oxaliplatin (50 mg/m2/wk) and 5-fluorouracil (200 mg/m2 in 5 daily continuous infusion). RESULTS: A total of 26 patients were included. All patients completed the programmed CRT. Severe acute toxicity was recorded in 19.2% of cases. Conservative surgery was performed in 16 patients, and a pathologic complete response was achieved in 19.2%. Overall, 26.9% of the patients died. The 5-year overall survival and disease-free survival rates were 70.6% and 65.5%, respectively. CONCLUSIONS: Intensified neoadjuvant CRT is an efficacious and safe treatment option for LARC in elderly patients.