Retrospective evaluation of the safety of low-level laser therapy/photobiomodulation in patients with head/neck cancer.

BACKGROUND: The standard therapeutic approach for locally advanced head and neck cancer is optimal use of radiation therapy with or without concomitant chemotherapy. The most common and distressing acute complication of such therapies is oral/pharyngeal mucositis that may be associated with severe morbidity and can interfere with the planned administration of therapy. METHODS: We have identified all patients diagnosed with head/neck cancer between 2005 and 2009, having received radiotherapy with or without cisplatin-based chemotherapy. Radiotherapy consisted of intensity-modulated radiation therapy (IMRT) in all patients. In patients with grade > 2 mucositis, photobiomodulation (PBM) consisted of three sessions of low-level laser irradiation weekly, in accordance with recently published recommendations for PBM. Patients who did not receive PBM were those for whom that approach was not requested by the radiotherapists and those who declined it. RESULTS: Two hundred twenty-two patients (62%) received PBM and 139 did not (39%). The patient's characteristics were equally distributed between the two groups. For overall survival, time to local recurrence, and progression-free survival, there was no statistical evidence for a difference in prognosis between patients with and without PBM. In a multivariate analysis, after adjusting for known prognostic factors, we found no statistical evidence that PBM was related to overall survival, progression-free survival, or local recurrence. CONCLUSIONS: Our results show evidence of no effect of PBM upon overall survival, time to local recurrences, and disease-free survival of patients with head and neck cancer treated with radiotherapy with/without chemotherapy.

Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN).

Background: To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR). Results: Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type. Conclusion: Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity. Clinical trial registration: ClinicalTrials.gov: NCT01538381.

[Nasopharyngeal adenoid cystic carcinoma, a rare but highly challenging disease with unmet therapeutic needs: A case-report and review of the literature]. / Carcinome adénoïde kystique du nasopharynx, une entité clinique rare en quête d'innovations thérapeutiques : cas clinique et revue de la littérature.

Nasopharyngeal adenoid cystic carcinoma is a rare tumour. Compared with others nasopharyngeal tumours, it is characterised by slow evolution but it is locally aggressive and has a high tendency to recurrences. Due to the rarity of cases, no consensus exists about treatment approaches. We report the case of 45-year-old-man with a locally advanced adenoid cystic carcinoma. The patient received concurrent chemoradiation and had a good objective response. After one year, he developed a paucisymptomatic lung metastasis. The follow-up showed local recurrence after 3 years. One cycle of chemotherapy was given but poorly supported. Carbon ion radiotherapy was proposed. The aim of this work is to review the literature concerning this rare malignancy and discusses treatment approaches in initial situations and during recurrences.

Innovative perspectives of immunotherapy in head and neck cancer. From relevant scientific rationale to effective clinical practice.

It is now well established that head and neck cancer carcinogenesis is characterized by genetic instability and several immune defects, leading to unique host-tumor interactions. In such condition, recent improved comprehension and relevant findings could lead to identification of innovative molecular therapeutic targets, achieving considerable clinical and translational research. This review aims to summarize and to highlight most recent and relevant scientific rationale in this era of immunotherapy revival, and to correlate it to the near future clinical practice for the management of this challenging disease.

A proof of concept trial of the anti-EGFR antibody mixture Sym004 in patients with squamous cell carcinoma of the head and neck.

PURPOSE: The purpose of the trial was to assess the efficacy and tolerability of Sym004, a novel 1:1 mixture of two chimeric monoclonal antibodies (992 and 1024) targeting non-overlapping epitopes of the anti-epidermal growth factor receptor (EGFR), in patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: Incurable, recurrent and/or metastatic SCCHN patients with acquired resistance to anti-EGFR monoclonal antibody-containing treatment received weekly infusions of 12 mg/kg Sym004 until disease progression or unacceptable toxicity. RESULTS: Among the 26 patients treated with Sym004, the proportion of patients alive without disease progression at 6 months was 12 % (95 % CI 1-39 %). The median duration of progression-free survival was 82 days (95 % CI 41-140 days). Of 19 patients evaluable for response, eight showed a decrease in the sum of the largest diameter in their target lesions (median 11 %; range 7-27 %). The best overall response was stable disease in 13 patients (50 %). Paired biopsies showed a significant down-regulation of EGFR in both skin and tumors following exposure to Sym004. All patients had EGFR-related adverse events, including grade 3 skin toxicities and grade ≥3 hypomagnesemia reported in 13 (50 %) and 10 (38 %) of 26 patients, respectively. One event fulfilling the protocol-defined criteria for infusion-related reactions (grade 2) was reported. No anti-drug antibodies were detected. CONCLUSIONS: The marked EGFR down-regulation shown in target tissues supports the proposed mechanism of action of Sym004. This trial revealed modest anti-tumor activity of Sym004 in extensively pretreated advanced SCCHN patients.

Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM trial.

BACKGROUND: Brain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the combination of both drugs as treatment for patients with HER2-positive BC and BM. METHODS: Eighteen patients were enrolled, with sixteen of them having recurrent or progressive BM. Any type of previous therapy was allowed, and disease was assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The primary end points were the evaluation of the dose-limiting toxicities (DLTs) and the determination of the maximum-tolerated dose (MTD). The secondary end points included objective response rate, clinical benefit and duration of response. RESULTS: The lapatinib-temozolomide regimen showed a favorable toxicity profile because the MTD could not be reached. The most common adverse events (AEs) were fatigue, diarrhea and constipation. Disease stabilization was achieved in 10 out of 15 assessable patients. The estimated median survival time for the 16 patients with BM reached 10.94 months (95% CI: 1.09-20.79), whereas the median progression-free survival time was 2.60 months [95% confidence interval (CI): 1.82-3.37]. CONCLUSIONS: The lapatinib-temozolomide combination is well tolerated. Preliminary evidence of clinical activity was observed in a heavily pretreated population, as indicated by the volumetric reductions occurring in brain lesions.

Combined ipsilateral treatment of cervical lymph nodes metastases from an unknown primary.

INTRODUCTION: The management of squamous cell carcinoma in undetermined primary tumours in the head and neck region (approximately 5.5% of patients) is controversial. MATERIAL AND METHODS: The present report examines the outcomes for 14 patients after an initial treatment strategy directed principally at the side of the neck that is clinically involved. The distribution of nodal status was as follows: 1 N1, 8 N2A, 4 N2B, and 1 N3. RESULTS: Initial treatment included a modified neck dissection in 12 cases and radical neck dissection in 2 cases, plus postoperative radiation in 10 cases. Radiotherapy was directed at the ipsilateral side of the neck alone. Concomitant radiochemotherapy was given in 2 cases. The rate of disease control on the ipsilateral side was 12/14. Two patients were treated by chemotherapy but died of their disease. The failure rate on the contralateral side was 2/14. These two patients were successfully salvaged. During follow-up, a primary tumour was detected in one case. At the end of the follow-up, 10 patients were alive. CONCLUSIONS: Modified radical neck dissection combined with postoperative radiation with or without chemotherapy could be considered in N1-N3 lymph node status. Despite generally advanced disease at presentation, patients presenting with cervical metastasis from an unknown primary carcinoma have a reasonable survival expectation and aggressive treatment is warranted. Careful follow-up is required for effective salvage treatment.

[Interest of the chest CT scanning in head and neck cancer]. / Intérêt du scanner thoracique dans le bilan initial et le suivi des patients traités pour un cancer des voies aérodigestives supérieures.

INTRODUCTION: The overall survival rate for patients with head and neck squamous cell carcinoma remains disappointingly static despite improved locoregional control. This has been attributed to the development of distant metastases and second primary malignancies in these patients, a large proportion of which occur in the thorax. The goal of this study is to determine the incidence of newly thoracic malignancies diagnosed initially and during the follow-up in head and neck patients by chest computed tomography. METHODS: We retrospectively analysed the incidence of thoracic malignancies in 77 patients presented newly diagnosed cancer of the head and neck. RESULT: 15/77 patients were found to have thoracic malignancies. In 10/77 patients (14%) the diagnosis was made at the same time that the initial head and neck cancer In 5/77 patients, the thoracic malignancies were diagnosed during the follow-up. In 3 of the 5 cases, the pulmonary lesion was diagnosed in patients with local recurrent tumours. The primary site or the stage had an effect on the incidence of simultaneous thoracic malignancies. CONCLUSION: The presence of distant metastases and second primary malignancies has major implications in the management and prognosis of patients presenting with head and neck carcinoma. We recommend a CT scanning of the thorax in the staging of patients presenting with head and neck cancer but also in the follow-up, particularly in patients with an advanced pharyngolaryngeal cancer.

Can we predict the duration of chemotherapy-induced neutropenia in febrile neutropenic patients, focusing on regimen-specific risk factors? A retrospective analysis.

BACKGROUND: The aim of the study was to elaborate a predictive model for the duration of chemotherapy-induced neutropenia (CIN) allowing the identification of patients with a higher risk of complications, especially complicated febrile neutropenia, who might benefit from preventive measures. PATIENTS AND METHODS: A score ranging from 0 to 4 on the basis of expected CIN was attributed to each cytotoxic agent given as part of chemotherapy treatment in solid tumours for patients with febrile neutropenia (FN). The individual scores were combined into several overall scores. RESULTS: A total of 203 patients with FN were eligible for this retrospective analysis. We were able to identify two groups of patients with statistically different neutropenia durations with median durations until hematological recovery of ANC > or =0.5 and > or =1.0 x 10(9)/l, being respectively 6 versus 4 days (P = 0.03) and 8 versus 6 days (P = 0.01). CONCLUSIONS: The duration of neutropenia is directly influenced by the aggressiveness of the chemotherapy regimen. In this retrospective study, we were able to identify a group of patients who needed two more additional days to recover from grade 3 and grade 4 neutropenia, based on the degree of aggressiveness of the cytotoxic agents used.

Will the dark sky over advanced renal cell carcinoma soon become brighter?

Until recently, immunotherapy has been the most efficient treatment for advanced renal cell carcinoma, but clinical results are largely unsatisfactory. More promising agents are being developed as a result of an improved understanding of the biology of the disease. Several agents that target known biological abnormalities of the disease are now being tested in the clinic. This review describes the encouraging clinical results obtained to date with these new drugs or combinations of drugs.

A prospective randomised evaluation of G-CSF or G-CSF plus oral antibiotics in chemotherapy-treated patients at high risk of developing febrile neutropenia.

BACKGROUND: Febrile neutropenia (FN) remains a major dose-limiting complication among patients treated with chemotherapy. Haematopoietic colony stimulating factors (G-CSF and GM-CSF) made possible a significant improvement in the management of FN, both in the therapeutic and in the prophylactic approach. The use of antibiotic prophylaxis also permits a definite reduction of severe infections during neutropenia. Nevertheless, the possible role of these two interventions for secondary prevention of FN is still unclear. PATIENTS AND METHODS: We conducted a prospective randomised trial by comparing the efficacy of granulocyte-colony stimulating factor (G-CSF) and the association of G-CSF with oral antibiotics in the secondary prevention of FN. We included in our study those patients who, after an episode of FN, continued to be treated with the same chemotherapy without reduction of dose intensity. They were randomised into two groups: the first received G-CSF (group G; filgrastim, 5 microg/kg day), and the second was treated with an association of G-CSF and amoxicillin/clavulanate plus ciprofloxacin (group G/ACC). RESULTS: Forty-eight patients were randomised (group G: n=23 and group G/ACC: n=25). There was no recurrence of FN among the patients receiving G-CSF and only one episode in the combined therapy group (p=1). With regard to the side effects, there was no significant difference in the two groups. CONCLUSION: The use of G-CSF for the secondary prevention of FN is extremely effective and allows the maintenance of chemotherapy dose intensity. Our study showed that the addition of antibiotics does not seem to be required.

Activity of chemotherapy and immunotherapy on malignant mesothelioma: a systematic review of the literature with meta-analysis.

The role of chemotherapy for unresectable malignant mesothelioma is unclear. The aims of the present study were to evaluate the methodological quality of published papers relative to chemotherapy or immunotherapy in malignant mesothelioma and to aggregate, for trials having a similar methodology, the response rates in order to identify the most active chemotherapeutic drugs and regimens. The literature relative to this topic, published between 1965 and June 2001 was reviewed. A methodological qualitative evaluation was performed according to the European Lung Cancer Working Party scale, specifically designed for phase II trials. A study was considered as potentially positive if the upper limit of the 95% confidence interval (CI) of the response rate was greater than 20% and positive if the lower limit of the 95% CI was > 20%. Eighty-three studies (88 treatment arms) were eligible for the systematic review. Fifty-three arms were considered as positive or potentially positive. No statistically significant difference in the methodological quality was observed between negative and positive studies. Studies were aggregated in four groups according to the presence of cisplatin and/or doxorubicin in the treatment regimen. The combination of cisplatin and doxorubicin had the highest response rate (28.5%; P < 0.001). Cisplatin was the most active single-agent regimen. Our systematic qualitative and quantitative overview of the literature suggests that the most active chemotherapeutic regimen, in term of objective response rate, is the combination of cisplatin and doxorubicin and the best single-agent is cisplatin. The combination of these two drugs can be recommended as control arm for future randomised phase III trials.