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.

Anticancer effect of AZD2461 PARP inhibitor against colon cancer cells carrying wt or dysfunctional p53.

Colon cancer is one of the most common cancers, currently treated with traditional chemotherapies or alternative therapies. However, these treatments are still not enough effective and induce several side effects, so that the search of new therapeutic strategies is needed. The use of Poly-(ADP-ribose)-polymerase (PARP) inhibitors, although originally approved against BRCA-1 or BRCA-2 mutated cancers, has been extended, particularly in combination with other treatments, to cure cancers that do not display defects in DNA repair signaling pathways. The role of p53 oncosuppressor in the regulating the outcome of PARP inhibitor treatment remains an open issue. In this study, we addressed this topic by using a well-tolerated PARP 1/2/3 inhibitor, namely AZD2461, against colon cancer cell lines with different p53 status. We found that AZD2461 reduced cell proliferation in wtp53 and p53-/- cancer cells by increasing ROS and DNA damage, while R273H mutant (mut) p53 counteracted these effects. Moreover, AZD2461 improved the reduction of cell proliferation by low dose radiation (IR) in wtp53 cancer cells, in which a down-regulation of BRCA-1 occurred. AZD2461 did not affect cell proliferation of mutp53 colon cancer cells also in combination with low dose radiation, suggesting that only wt p53 or p53 null colon cancer cells could benefit AZD2461 treatment.

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.

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.

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.

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

BACKGROUND: Neoadjuvant fluoropirimidine (5FU)-based chemoradiotherapy (CRT) has been considered the standard of care for locally advanced rectal cancer (LARC). Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is still debated. We conducted a meta-analysis to evaluate the role of OXP in this patient population. METHODS: Literature searches were carried out in PubMed, Medline and Scopus databases. End points were overall survival (OS), disease free survival (DFS), local failure (LF) and distant failure (DF). Odd ratio (OR) with 95% confidence interval (CI) was calculated using random effects model. RESULTS: Four randomized trials were included. Patients treated with OXP-5FU CRT had significantly decreased DF (OR = 0.76; 95% CI, 0.60 to 0.97; p = 0.03) compared to standard CRT. OS, DFS and LF were not significantly different between groups. CONCLUSIONS: OXP significantly decreased DF, but does not improve OS e DFS compared to 5FU CRT. Precise role of OXP in neoadjuvant setting of LARC remains to be determined.

Relation between Hypofractionated Radiotherapy, Toxicity and Outcome in Early Breast Cancer.

To compare adjuvant conventional radiotherapy (C-RT) to hypofractionated schedule (HF-RT) in early breast cancer. Between May 2012 and September 2015, 120 patients were included in the analysis. All patients underwent conservative surgery and adjuvant RT. RT was delivered in C-RT (50 Gy; 2 Gy/fr) or HF-RT (42.5 Gy; 2.66 Gy/fr), followed by a tumor bed boost (10 Gy; 2 Gy/fr). RT-induced toxicity was recorded and compared between groups. Toxicity results were graded according to the Common Terminology Criteria for Adverse Events guidelines. A multivariate analysis was performed of the factors associated with acute toxicity onset. Mild acute skin toxicity was observed in 71.7% of patients. No grade 4 toxicity was observed. From the multivariate analysis, Breast volume and RT fractionation significantly affected acute radiation-related toxicity. No increase in late toxic effects has been reported between C-RT and HF-RT schedules. Overall, the 2-year disease free survival was 94.4%. HF-RT represents a valid adjuvant treatment option in early breast cancer patients, without negative impact on acute and late radiation sequelae, as well as tumor control.

Pulsed-Dose Rate Brachytherapy for the Treatment of Endometrial Cancer.

Endometrial cancer (EC) is the most frequent gynecologic malignancy. The aim of this review is to outline clinical practice recommendations, to suggest a technical solution, and to advise doses selection for pulsed-dose rate (PDR) brachytherapy in EC. Electronic bibliographic databases, including PubMed, clinicaltrials.gov, and the American Society of Clinical Oncology (ASCO) Meeting Library, were searched for articles in English. Clinical guidelines and systematic reviews were also considered. The appropriate therapeutic approach should consider risk factors for tumor relapse and PDR brachytherapy and have a convincing role in this multidisciplinary scenario. Performing PDR brachytherapy in EC requires robust training and experience.

Disease Control, Survival, and Toxicity Outcome After Intensified Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Single-Institution Experience.

PURPOSE: To report the long-term follow-up data and determine the toxicity rate concerning patients with locally advanced rectal cancer (LARC) treated with an intensified neoadjuvant treatment regimen. PATIENTS AND METHODS: Patients with histologically proven stage II to III adenocarcinoma of the rectum were included and treated with a trimodal approach. Intensified neoadjuvant treatment (chemoradiotherapy [CRT]) consisted of radiotherapy (total dose 50.4/54 Gy) and concomitant oxaliplatin (50 mg/m(2)/week) and 5-fluorouracil (200 mg/m(2)/5 daily continuous infusion). Surgery was planned 7 to 9 weeks after the end of CRT. Adjuvant chemotherapy was recommended in those patients with lymph node metastasis at diagnosis. RESULTS: One hundred patients (median age, 64 years) were eligible. Overall, the 5-year overall survival and disease-free survival (DFS) were 76.4% and 74.5%, respectively. CRT was well tolerated, with only 17% grade 3/4 acute toxicity. Twenty-four patients (24%) had a pathologic complete response (pCR), and only 1 patient had perioperative metastasis. The 5-year DFS were 95.7% and 66.7% for pCR and no-pCR tumor histology, respectively (P = .0275). CONCLUSION: Although oxaliplatin is not considered to be a standard treatment, the high 5-year rate of overall survival and DFS, the low severe toxicity rates, and the effective benefit on pCR and perioperative metastasis support an intensified treatment regimen for LARC.

Number of mediastinal lymph nodes as a prognostic factor in PN2 non small cell lung cancer: a single centre experience and review of the literature.

Currently the most important prognostic factor in lung cancer is the stage. In the current lung TNM classification system, N category is defined exclusively by anatomic nodal location though, in other type of tumours, number of lymph nodes is confirmed to be a fundamental prognostic factor. Therefore we evaluated the number of mediastinal lymph nodes as a prognostic factor in locally advanced NSCLC after multimodality treatment, observing a significant effect of the number of lymph nodes in terms of OS (p<0.01) and DFS (p<0.001): patients with a low number of positive mediastinal nodes have a better prognosis.

Two different intensity-modulated radiotherapy strategies for patients with high-risk prostate cancer.

AIM: To compare toxicity profiles of two different intensity-modulated radiation therapy (IMRT) strategies in patients with high-risk prostate cancer. PATIENTS AND METHODS: From May 2010 to September 2012, 43 patients with high-risk prostate cancer were treated with IMRT and concurrent hormone therapy; 23 patients were treated by conventional fractionation (IMRT/C) and 20 patients by simultaneous integrated boost (IMRT/SIB). Acute and late toxicities were compared for each group. RESULTS: Severe acute genitourinary toxicity was recorded in 8.6% and 2% of patients in the IMRT/C and IMRT/SIB group, respectively. Genitourinary toxicity G2 was observed in 39.1% (IMRT/C group) and 25% (IMRT/SIB group) of patients. Severe acute gastrointestinal toxicity was not observed; Grade 2 acute gastrointestinal toxicity was recorded in 21.7% (IMRT/C group) and 10% (IMRT/SIB group). Grade 2 late genitourinary toxicity was observed in 26% (IMRT/C group) and 15% (IMRT/SIB group), whereas G2 late gastrointestinal toxicity in 34.5% and 30% of patients, respectively. No significant differences in incidence and severity of genitourinary and gastrointestinal toxicity were detected between the two IMRT treatment strategies. CONCLUSION: IMRT/SIB was well-tolerated with favorable rates of acute and late toxicity, both genitourinary and gastrointestinal. Compared to IMRT/C, IMRT/SIB maintained the same efficacy and reduced the overall treatment time.

Multiple bone metastases from glioblastoma multiforme without local brain relapse: a case report and review of the literature.

Extracranial metastases from glioblastoma multiforme (GBM) are a very rare event, even if an increasing incidence has been documented. We report the case of a young woman with primary GBM who developed bone metastases without local brain relapse. Because of persistent headache and visual disturbances, in March 2011 the patient underwent magnetic resonance imaging (MRI) evidencing a temporoparietal mass, which was surgically resected. Histology revealed GBM. She was given concomitant chemoradiotherapy according to the Stupp regimen. After a 4-week break, the patient received 6 cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days. In December 2011 she complained of progressive low back pain, and MRI showed multiple bone metastases from primary GBM, confirmed by histology. Cases of metastatic GBM in concurrence with a primary brain tumor or local relapse are more common in the literature; only a few cases have been reported where extracranial metastases from GBM occurred without any relapse in the brain. Here we report our experience.

Neoadjuvant-intensified treatment for rectal cancer: time to change?

AIM: To investigate whether neoadjuvant-intensified radiochemotherapy improved overall and disease-free survival in patients with locally advanced rectal cancer. METHODS: Between January 2007 and December 2011, 80 patients with histologically confirmed rectal adenocarcinoma were enrolled. Tumors were clinically classified as either T3 or T4 and by the N stage based on the presence or absence of positive regional lymph nodes. Patients received intensified combined modality treatment, consisting of neoadjuvant radiation therapy (50.4-54.0 Gy) and infusional chemotherapy (oxaliplatin 50 mg/m(2)) on the first day of each week, plus five daily continuous infusions of fluorouracil (200 mg/m(2) per die) from the first day of radiation therapy until radiotherapy completion. Patients received five or six cycles of oxaliplatin based on performance status, clinical lymph node involvement, and potential risk of a non-sphincter-conserving surgical procedure. Surgery was planned 7 to 9 wk after the end of radiochemotherapy treatment; adjuvant chemotherapy treatment was left to the oncologist's discretion and was recommended in patients with positive lymph nodes. After treatment, all patients were monitored every three months for the first year and every six months for the subsequent years. RESULTS: Of the 80 patients enrolled, 75 patients completed the programmed neoadjuvant radiochemotherapy treatment. All patients received the radiotherapy prescribed total dose; five patients suspended chemotherapy indefinitely because of chemotherapy-related toxicity. At least five cycles of oxaliplatin were administered to 73 patients. Treatment was well tolerated with high compliance and a good level of toxicity. Most of the acute toxic effects observed were classified as grades 1-2. Proctitis grade 2 was the most common symptom (63.75%) and the earliest manifestation of acute toxicity. Acute toxicity grades 3-4 was reported in 30% of patients and grade 3 or 4 diarrhoea reported in just three patients (3.75%). Seventy-seven patients underwent surgery; low anterior resection was performed in 52 patients, Miles' surgery in 11 patients and total mesorectal excision in nine patients. Fifty patients showed tumor downsizing ≥ 50% pathological downstaging in 88.00% of tumors. Out of 75 patients surviving surgery, 67 patients (89.33%) had some form of downstaging after preoperative treatment. A pathological complete response was achieved in 23.75% of patients and a nearly pathologic complete response (stage ypT1ypN0) in six patients. An involvement of the radial margin was never present. During surgery, intra-abdominal metastases were found in only one patient (1.25%). Initially, 45 patients required an abdominoperineal resection due to a tumor distal margin ≤ 5 cm from the anal verge. Of these patients, only seven of them underwent Miles' surgery and sphincter preservation was guaranteed in 84.50% of patients in this subgroup. Fourteen patients received postoperative chemotherapy. In the full analysis of enrolled cohort, eight of the 80 patients died, with seven deaths related to rectal cancer and one to unrelated causes. Local recurrences were observed in seven patients (8.75%) and distant metastases in 17 cases (21.25%). The five-year rate of overall survival rate was 90.91%. Using a median follow-up time of 28.5 mo, the cumulative incidence of local recurrences was 8.75%, and the overall survival and disease-free survival rates were 90.00% and 70.00%, respectively. CONCLUSION: The results of this study suggest oxaliplatin chemotherapy has a beneficial effect on overall survival, likely due to an increase in local tumor control.

An unusual case of fatty liver in a patient with desmoid tumor.

A desmoid tumor, also known as aggressive fibromatosis, is a rare benign neoplasm that arises from fascial or musculoaponeurotic tissues. It can occur in any anatomical location, most commonly the abdominal wall, shoulder girdle and retroperitoneum. The typical clinical presentation is a painless mass with a slow and progressive invasion of contiguous structures. It is associated with a high local recurrence rate after resection. Many issues regarding the optimal treatment of desmoid tumors remain controversial. Aggressive surgical resection with a wide margin (2-3 cm) remains the gold standard treatment with regard to preserving quality of life. Radiotherapy alone has been shown to be effective for the control of unresectable or recurrent lesions. Desmoid tumors tend to be locally infiltrative, therefore, the fields must be generous to prevent marginal recurrence. The radiation dose appropriate for treating desmoid tumors remains controversial. We present a 25-year-old Caucasian man with local recurrence of a desmoid tumor after repeated surgical resection, treated with radiotherapy. The patient achieved complete tumor regression at 4 mo after radiotherapy, and he is clinically free of disease at 12 mo after the end of treatment, with an acceptable quality of life. The patient developed short bowel syndrome as a complication of second surgical resection. Consequently, radiotherapy might have worsened an already present malabsorption and so led to steatohepatitis.

Preoperative intensified radiochemotherapy for rectal cancer: experience of a single institution.

PURPOSE: The aim of our study was to evaluate the feasibility and the effectiveness of an intensified neoadjuvant protocol with the addition of weekly oxaliplatin in the preoperative strategy of rectal cancer treatment. PATIENTS AND METHODS: Patients with locally advanced rectal cancer received continous infusion 5-Fluorouracil (5-FU) 200 mg/m(2)/day in combination with weekly oxaliplatin at a dose of 50 mg/m(2). Doses of radiotherapy were 45 Gy to the whole pelvis plus 5.4-9 Gy to the tumour mass. The primary end-points of the study were evaluation of toxicity, compliance with radiotherapy and chemotherapy, downstaging, pathological complete response (pCR) and the rate of sphincter preservation for distal cancers. Secondary end-points were relapse-free and overall survival. RESULTS: From November 2006 to June 2009, 51 patients were enrolled into the study. Compliance with chemotherapy was 80%. The incidence of G3 diarrhoea and proctitis were 17.6% and 21.5%, respectively. Surgery was performed in 48 patients with 100% R0 resection. 76.4% of low-lying tumours underwent conservative treatment. Seventy-nine percent of patients were downstaged: T and N downstaging were observed in 71% and 75% of patients, respectively. A pCR was obtained in 11 (22.9%) patients. CONCLUSIONS: Intensification of neoadjuvant treatment for rectal cancer with the addition of weekly oxaliplatin is feasible, with remarkable rates of downstaging and pathological complete response. Data on sphincter preservation for distal cancers were excellent. Phase III trials with a longer follow-up will establish whether this good outcome in terms of surrogate end-points will translate into better rates of disease-free and overall survival.

Chemoradiation as definitive treatment for primary squamous cell cancer of the rectum.

In this report, we present a case of advanced squamous cell cancer located in the rectum of a 78-year-old woman treated with chemoradiation with curative intent. The patient showed a complete clinical response to chemoradiation; multiple biopsies were performed at the site of the previous mass 5 mo after the end of treatment and histological examination showed no residual tumour in the specimens. Surgical intervention was avoided and the patient was free of disease 12 mo after the diagnosis of cancer. Primary chemoradiation should be considered as the treatment of choice for this rare malignancy.

Comparison between intensified neoadjuvant treatment and standard preoperative chemoradiation for rectal cancer.

OBJECTIVES: The aim of the current study was to compare a neoadjuvant regimen containing oxaliplatin with standard preoperative treatment for rectal cancer. METHODS: From December 2006 to December 2007, 20 patients with rectal cancer were treated at our Institution with the weekly addition of oxaliplatin (50 mg/m(2)) to radiotherapy (50.4-54.0 Gy in 28-30 daily fractions) and continuous infusion of 5-fluorouracil (200 mg/m(2)). The results of the regimen were compared with a historical control group including 21 consecutive patients previously treated with standard 5-fluorouracil treatment from December 2004 to October 2006. RESULTS: Both the rate of sphincter preservation in low rectal cancer (91.7% vs 36.4%, P = 0.009) and the rate of downstaging (84.2% vs 47.6%, P = 0.023) were higher in the oxaliplatin group than in the control group. Pathological complete response was achieved in 8 patients (42.1%) in the oxaliplatin group and in 4 patients (19.0%) in the control group (P = 0.172). When ypT0-pT1 stages were analyzed together, the P value was 0.051. Acute toxicity was increased in the oxaliplatin group, with a higher incidence of G3 diarrhea and pelvic pain than in the control group (30.0% vs 14.3%, P = NS). CONCLUSIONS: Our data seem to correlate the addition of oxaliplatin to the standard treatment for rectal cancer with higher rates of sphincter preservation, down-staging and complete response. Toxicity is increased and requires careful monitoring. However, our results refer to a retrospective comparison of a small series of patients and need to be validated by the large, phase III randomized trial currently ongoing.