Oligo metastatic renal cell carcinoma: stereotactic body radiation therapy, if, when and how?

BACKGROUND AND PURPOSE: Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity. PATIENTS AND METHODS: A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan-Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy. RESULTS: From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10-52) in 5-10 fractions. With a median follow-up of 2.3 years (range 0-7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No > G1 acute and late toxicities were reported. CONCLUSION: The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.

Radiation-induced acute dysphagia : Prospective observational study on 42 head and neck cancer patients.

PURPOSE: Acute toxicity in head and neck (H&N) cancer patients treated with definitive radiotherapy (RT) has a crucial role in compliance to treatments. The aim of this study was to correlate doses to swallowing-associated structures and acute dysphagia. METHODS: We prospectively analyzed 42 H&N cancer patients treated with RT. Dysphagia (grade ≥ 3) and indication for percutaneous endoscopic gastrostomy (PEG) insertion were classified as acute toxicity. Ten swallowing-related structures were considered for the dosimetric analysis. The correlation between clinical information and the dose absorbed by the contoured structures was analyzed. Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for normal tissue complication probability (NTCP) modelling. RESULTS: A strong multiple correlation between dosimetric parameters was found. A two-variable model was suggested as the optimal order by bootstrap method. The optimal model (Rs = 0.452, p < 0.001) includes V45 of the cervical esophagus (odds ratio [OR] = 1.016) and Dmean of the cricopharyngeal muscle (OR = 1.057). The model area under the curve was 0.82 (95% confidence interval 0.69-0.95). CONCLUSION: Our results suggested that the absorbed dose to the cricopharyngeal muscle and cervical esophagus might play a relevant role in the development of acute RT-related dysphagia.

A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose cisplatin.

BACKGROUND: The activity of ginger in the management of chemotherapy-induced nausea and vomiting (CINV) has been suggested, but design inadequacies, heterogeneity of the population, small numbers and poor quality of tested products limit the possibility to offer generalizable results. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter study in patients planned to receive ≥2 chemotherapy cycles with high dose (>50 mg/m2) cisplatin. Patients received ginger 160 mg/day (with standardized dose of bioactive compounds) or placebo in addition to the standard antiemetic prophylaxis for CINV, starting from the day after cisplatin administration. CINV was assessed through daily visual-analogue scale and Functional Living Index Emesis questionnaires. The main objective was protection from delayed nausea; secondary end points included intercycle nausea and nausea anticipatory symptoms. RESULTS: In total, 121 patients received ginger and 123 placebo. Lung (49%) and head and neck cancer (HNC; 35%) were the most represented tumors. No differences were reported in terms of safety profile or compliance. The incidence of delayed, intercycle and anticipatory nausea did not differ between the two arms in the first cycle and second cycle. A benefit of ginger over placebo in Functional Living Index Emesis nausea score differences (day 6-day 1) was identified for females (P = 0.048) and HNC patients (P = 0.038). CONCLUSIONS: In patients treated with high-dose cisplatin, the daily addition of ginger, even if safe, did not result in a protective effect on CINV. The favorable effect observed on nausea in subgroups at particular risk of nausea (females; HNC) deserves specific investigation.

Feasibility of concurrent chemoradiotherapy with high-dose cisplatin after induction TPF chemotherapy in head and neck cancer: a critical review of the literature and the experience of the European Institute of Oncology.

Many concerns are related to the idea that the acute toxicity of induction chemotherapy (IC) performed with TPF (docetaxel, cisplatin, 5-fluorouracil) could reduce the ability to deliver the subsequent standard concurrent chemoradiotherapy (CRT) in head and neck cancer patients. We performed a critical review of the literature on the toxicity profile of the standard CRT administered after the IC with TPF. A total of 13 papers (including 950 patients) were selected. Results showed that most patients were treated with an adequate radiation total dose although a significant proportion of them (from 15 to 30%) completed the planned treatment with a delay of more than 5 days. A minority of patients were able to be treated with three cycles of concurrent cisplatin, but only few papers reported how many of patients reached the cumulative total dose of almost 200 mg/m2 cisplatin. The rate of deaths due to treatment-related toxicity varied from 0 to 9% (median and mean 2%). Two prospective trials stopped patient enrollment due to acute treatment-related toxicity and because a low number of patients were able to undergo the planned full schedule of cisplatin during the CRT, respectively. Retrospective analysis of 45 patients treated at our institute showed that this schedule was feasible with manageable side effects. In conclusion, the literature data did not provide homogeneous information on the feasibility of the standard CRT after induction TPF. A more uniform data collection of treatment-related toxicity will be helpful in better selecting the patients who might adequately tolerate this multimodality strategy.

Non-surgical organ preservation strategies for locally advanced laryngeal tumors: what is the Italian attitude? Results of a national survey on behalf of AIRO and AIOM.

Chemoradiotherapy is the treatment mostly used as organ preservation (OP) strategy worldwide in advanced laryngo-hypopharyngeal cancer. Due to the not homogeneous results of the literature data regarding the pre-treatment assessment and treatment schedule in this setting of patients, the Italian societies of radiation oncology and medical oncology surveyed (by an online survey) their memberships regarding the Italian attitude on larynx preservation in clinical practice. The survey outline addressed different items such as: demographics (11 items), pre-treatment evaluation (12 items), treatment schedules (10 items) and outcomes (3 items). The survey was filled in by 116 clinical oncologists (64 % radiation and 36 % medical oncologists). Results highlighted that pretreatment evaluation was not homogeneous among the respondents. The treatment of choice for the OP program resulted the concurrent chemoradiotherapy (66 %). Induction chemotherapy was proposed mostly in case of aggressive tumors such as advanced stage (T4 or N3) and/or unfavorable primary sites (hypopharynx). Moreover, after induction chemotherapy, for responders patients most participants (46 %) proposed concurrent chemoradiotherapy, while 18 and 19 % proposed radiotherapy alone or radiotherapy and cetuximab, respectively. For patients with stable disease after induction chemotherapy, the respondents declared to suggest surgery, radiotherapy and cetuximab or radiotherapy alone in 38, 32 and 15 % of cases, respectively. Results of the present survey highlighted the variability of therapeutic approaches offered in clinical practice for patients candidate to a larynx OP program. Analysis of abovementioned results may give the chance to modify some clinical attitudes and create the background for future clinical investigation in this field.

Metronomic administration of pegylated liposomal-doxorubicin in extensively pre-treated metastatic breast cancer patients: a mono-institutional case-series report.

BACKGROUND: Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. Pegylated liposomal-doxorubicin (PLD) pharmacokinetic characteristics support the rationale for using the drug in a metronomic fashion, potentially able to combine anthracyclines efficacy to a low toxicity profile. PATIENTS AND METHODS: In a case-series report carried out in both anthracycline-naive and pre-treated metastatic breast cancer patients, we tested feasibility, clinical efficacy and tolerability of PLD administered with a novel metronomic schedule of 20mg/m(2) i.v. every two weeks. RESULTS: 52 patients were enrolled and 45 were evaluated. Forty-four patients were assessed for either response or toxicity. Eight patients (18%) had partial responses (PR) and 17 (39%) stable disease (SD), with a clinical benefit (CB) of 45% (95% CI: 30.3%-59.7%). Nineteen patients (43%) had progressive disease (PD). Neither grade 3 nor grade 4 haematological or clinical side effects were recorded, except for 2 patients with grade 3 palmar-plantar erythrodysesthesia (PPE). No cardiac toxicity was recorded. CONCLUSION: Metronomic administration of PLD is a feasible and active treatment for extensively pre-treated metastatic breast cancer patients, alternative to classic anthracyclines, balancing clinical efficacy with a good quality of life in terms of reduced side effects and low personal costs for the patient.

Cisplatin, etoposide and continuous infusion bleomycin in patients with testicular germ cell tumors: efficacy and toxicity data from a retrospective study.

We retrospectively reviewed medical charts of 54 patients who underwent orchidectomy for germ cell tumors (GCT) and received a regimen, given every 3 weeks, consisting of cisplatin 100 mg/m2 day 4 intravenous (i.v.), bleomycin 15 Units (U) day 1 i.v. push; bleomycin 10 U days 1-3 24 h i.v. continuous infusion (c.i.) and etoposide 100 mg/m2 days 1-5/i.v. (PEB). 53 of 54 patients achieved a complete remission without adjunctive surgery. At a median follow-up of 48.2 months (95%CI 41.7 - 54.8 months) all patients but one are alive with no evidence of disease recurrence. Patients receiving PEB experienced no pulmonary toxicity, nephrotoxicity nor neurological adverse events. PEB with c.i.bleomycin is an active regimen with a low rate of acute and late toxicity. The main limitations of our study are related to the retrospective analysis, the limited number of patients and the restricted follow-up time. A prolonged follow-up is necessary to evaluate long term toxicity and outcome.

Brain metastases in patients with advanced breast cancer.

BACKGROUND: The incidence of brain metastases (BM) is apparently rising in patients with advanced breast cancer (ABC). We performed a case control study to define current features of breast cancer related to central nervous system (CNS) metastases. PATIENTS AND METHODS: From March 1999 to May 2006, we identified 72 patients with symptomatic BM of breast cancer. A comparison group was randomly selected assigning to each case two patients with primary breast cancer and no BM, matched for year of diagnosis, age and tumour stage (pT status and nodal status). RESULTS: Cases had a significantly higher rate of negative estrogen receptors (ERs) (60% in cases vs. 29% in controls), negative progesterone receptors (PgRs) (79% vs. 43%), HER2/neu over expression (44% vs. 13%) and immunostaining for Ki-67 > or =20% (84% vs. 55%), with p-value <0.001 for all four parameters in univariate analyses. On multivariate analysis, HER2/neu over expression and Ki-67 -20% were independent predictive factors of brain relapse (Odds Ratio (OR) 2.55, 95% confidence intervals (CI) 1.10-5.94 and OR 2.97, 95% CI 1.01-8.73, respectively). Endocrine unresponsive tumours (both ER and PgR <10%) showed an increased risk of relapse with BM of borderline significance (OR 1.91, 95% CI 0.87-4.12). CONCLUSION: Patients with ER and PgR negative tumours either with or without HER-2/neu over expression should be considered at higher risk of BM.

Bisphosphonates and jaw osteonecrosis in patients with advanced breast cancer.

BACKGROUND: In recent years, several cases of mandibular necrosis associated with long-term use of bisphosphonates have been reported. The estimated incidence varies from 1% to 4.6%. PATIENTS AND METHODS: We conducted an observational study with the aim of determining the incidence of jaw osteonecrosis in advanced breast cancer patients with bone metastases under bisphosphonate treatment and to identify subjects at higher risk of developing this complication evaluating preclinical signs. We considered two groups of patients. All the patients complaining of odontostomatological symptoms underwent maxillary CT scan and maxillo-surgeon clinical examination. Asymptomatic patients were asked to perform a standard orthopantomography (OPT). RESULTS: From February 2005 to October 2005, we observed five patients with jaw bone necrosis (6%). Diagnosis was radiological and clinical. In two patients a confirmatory biopsy was performed. In the same time interval, OPTs were collected from 76 asymptomatic patients. Three OPTs revealed radiological features of suspicious mandibular necrosis. Maxillary CT scan confirmed the presence of an osteolityc area with signs of periosteal reaction. All the three patients were referred to maxillo-surgeon and two out of three patients underwent mandibular biopsy, but histopathological results were not conclusive. CONCLUSIONS: In our experience, the incidence of jaw bone necrosis in breast cancer patients seems to be higher than in other reports (6%). Radiological features of suspicious jaw necrosis were observed in three asymptomatic patients. We do not know how these findings should be considered. Anyway, standard OPT is a simple procedure, and may allow identification of periodontal conditions that in some way can predispose to the development of this uncommon event.