Marta Maddalo

Cetuximab and Radiotherapy Versus Cisplatin and Radiotherapy for Locally Advanced Head and Neck Cancer: A Randomized Phase II Trial

PURPOSE No randomized trials have been conducted to directly compare radiotherapy (RT) with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced squamous cell carcinoma of the head and neck. In this randomized trial, we compared these two treatment regimens in terms of compliance, toxicity, and efficacy. PATIENTS AND METHODS Eligible patients were randomly assigned in a 1:1 ratio to receive either CDDP 40 mg/m(2) once per week or CTX 400 mg/m(2) as loading dose followed by CTX 250 mg/m(2) once per week concomitant to radical RT. For primary end points, compliance to treatment was defined as number of days of treatment discontinuation and drug dosage reduction. The acute toxicity rate was defined according to the National Cancer Institute Common Toxicity Criteria. Efficacy end points were local recurrence-free survival, metastasis-free survival, cancer-specific survival, and overall survival. RESULTS The study was discontinued early because of slow accrual after the enrollment of 70 patients. RT discontinuation for more than 10 days occurred in 13% of patients given CTX and 0% given CDDP (P = .05). Drug dosage reduction occurred in 34% given CTX and 53% given CDDP (difference not significant). Toxicity profiles differed between the two arms, with hematologic, renal, and GI toxicities more frequent in the CDDP arm, and cutaneous toxicity and the need for nutritional support more frequent in the CTX arm. Serious adverse events related to treatment, including four versus one toxic deaths, were higher in the CTX arm (19% v 3%, P = .044). Locoregional control, patterns of failure, and survivals were similar between the treatment arms. CONCLUSION CTX concomitant to RT lowered compliance and increased acute toxicity rates. Efficacy outcomes were similar in both arms. These results raise the issue of appropriately selecting patients with head and neck cancer who can benefit from CTX in combination with RT.

Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Dental pathologies and osteoradionecrosis (Part 1) literature review and consensus statement

Radiotherapy alone or in combination with chemotherapy and/or surgery is the typical treatment for head and neck cancer patients. Acute side effects (such as oral mucositis, dermatitis, salivary changes, taste alterations, etc.), and late toxicities in particular (such as osteo-radionecrosis, hypo-salivation and xerostomia, trismus, radiation caries etc.), are often debilitating. These effects tend to be underestimated and insufficiently addressed in the medical community. A multidisciplinary group of head and neck cancer specialists met in Milan with the aim of reaching a consensus on clinical definitions and management of these toxicities. The Delphi Appropriateness method was used for developing the consensus, and external experts evaluated the conclusions. This paper contains 10 clusters of statements about the clinical definitions and management of head and neck cancer treatment sequels (dental pathologies and osteo-radionecroses) that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecroses (10 clusters of statements), whereas this second part deals with trismus and xerostomia.

Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Xerostomia and trismus (Part 2). Literature review and consensus statement.

Radiotherapy alone or in combination with chemotherapy and/or surgery is a well-known radical treatment for head and neck cancer patients. Nevertheless acute side effects (such as moist desquamation, skin erythema, loss of taste, mucositis etc.) and in particular late toxicities (osteoradionecrosis, xerostomia, trismus, radiation caries etc.) are often debilitating and underestimated. A multidisciplinary group of head and neck cancer specialists from Italy met in Milan with the aim of reaching a consensus on a clinical definition and management of these toxicities. The Delphi Appropriateness method was used for this consensus and external experts evaluated the conclusions. The paper contains 20 clusters of statements about the clinical definition and management of stomatological issues that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecrosis (10 clusters of statements), whereas this second part deals with trismus and xerostomia (10 clusters of statements).

Reirradiation in head and neck recurrent or second primary tumor: efficacy, safety, and prognostic factors

Aims and background We investigated efficacy, safety, and prognostic factors of reirradiation in patients with recurrent or second primary head and neck cancer. Methods Records of 75 consecutive patients treated with reirradiation between August 2005 and December 2013 were reviewed. Results Median overall survival (OS) and cancer-specific survival (CSS) were 29.5 and 33.6 months. Median local control (LC) and progression-free survival (PFS) were 21.7 and 16.2 months. Univariate analysis showed that patients younger than 70 years, with a Karnofsky Performance Status (KPS) >90 or with 2 or less comorbidities at time of reirradiation, have a better OS; KPS >90 and biological equivalent dose (BED) >72 Gy positively influenced the PFS. At multivariate analysis, KPS at reirradiation was an independent predictive factor for OS, while BED was an independent predictive factor for CSS and OS. At univariate analysis, patients with planning target volume (PTV) >221 mL had worse LC and PFS rates, with results confirmed at multivariate analysis. The rate of fatal treatment-related adverse events was 6.7% (3 carotid blowout, 1 soft tissue necrosis, and 1 thromboembolic event). Conclusions This study confirms the role and outcomes of reirradiation. A careful selection of patients could minimize acute and late side effects and influence survival: elderly patients, with significant medical comorbidities or poor KPS, are worse candidate for reirradiation. Total dose delivered with reirradiation and PTV appear to be other potential prognostic factors. Further studies of dose escalation are needed to establish the total dose that could achieve better LC rates with a safer toxicity profile.

External beam radiotherapy ± chemotherapy in the treatment of anal canal cancer: a single-institute long-term experience on 100 patients.

One-hundred patients treated with curative radiotherapy (RT) ± chemotherapy (CT) for an anal canal carcinoma (T1–4N0–3M0) were retrospectively analyzed. Five- and 10-year local control (LC) rates were 73% and 67%, respectively. Acute and late G3–G4 toxicity rates were 32% and 12%, respectively. Two patients underwent a colostomy for a G4 anal toxicity. This study confirms the outcomes of RT ± CT in the treatment of anal canal cancer. Concomitant CT and LC statistically influenced Overall Survival and Colostomy-Free Survival. CT also statistically reduced the risk of nodal relapse. High rates of acute skin toxicity impose tailored volumes and techniques of irradiation.

What is the role of postoperative re-irradiation in recurrent and second primary squamous cell cancer of head and neck? A literature review according to PICO criteria

Re-irradiation has been increasingly offered as a potential effective treatment for head and neck squamous cell carcinoma (HNSCC) loco-regional recurrence as well as second primary tumor in previously irradiated area. This review focused on the role of postoperative re-irradiation (POreRT) in terms of feasibility, toxicity and long-term outcomes in HNSCC patients. The key issue for the research was formulated in two questions according to the PICO (population, intervention, control, and outcomes) criteria. A total of 16 publications met the inclusion criteria for a total of 919 patients; in 522 patients POreRT was performed. POreRT in recurrent and second primary HNSCC seems to be feasible in highly selected patients with the intent to guarantee an acceptable LC compared to surgery alone. The optimal RT schedule remains unclear due to the heterogeneity of literature data.

Could Concomitant Radio-Chemotherapy Improve the Outcomes of Early-Stage Node Negative Anal Canal Cancer Patients? A Retrospective Analysis of 122 Patients

One hundred twenty-two early-stage anal canal cancer patients (median age: 69 years) were treated with curative radiotherapy with (70 patients) or without (52 patients) concomitant chemotherapy. Median follow-up was 65 months (range: 4–238). At multivariate analysis, concomitant chemotherapy significantly improved local control (p = .007). Local control significantly influenced all considered endpoints, except the metastases free survival. The global rates of G3–G4 acute and late toxicity were 13.1% and 8.2%, respectively, and they were not increased by concomitant chemotherapy. Finally, concomitant chemotherapy is efficacious and safe in the treatment of T1-2N0 anal canal cancer patients and should be prospectively studied.

Re-irradiation with curative intent in patients with squamous cell carcinoma of the head and neck: a national survey of usual practice on behalf of the Italian Association of Radiation Oncology (AIRO)

AbstractObjectiveTo report the results of a national survey investigating the pattern of practice of curative re-irradiation (ReRT) for recurrent squamous cell carcinoma of the head and neck.MethodsIn March 2016, a 22-item, 4-section questionnaire was sent to all Italian Radiation Oncology centers. Sections were focused on assessing the expertise level of each center and collecting specific information on reRT prescription modalities in the adjuvant and definitive settings.ResultsOverall, 77 centers completed the survey. The majority (50/77, 64.9%) of participating radiation oncologists were senior consultants (> 10 years of experience). Of the responding centers, 63 (81.8%) performed curative ReRT, while 14 (18.1%) did not, mainly (5/14, 35.7%) due to the avoidance of severe toxicity. The use of adjuvant ReRT was reported by less than half of the interviewed radiation oncologists (36/77, 46.7%). In case of unresectable local recurrence, definitive ReRT was claimed to be adopted in 55/77 (71.4%) for non-nasopharyngeal and 47/77 (61%) for nasopharyngeal cancer. The preferred treatment technique was Intensity Modulated Radiation Therapy (IMRT) followed by Stereotactic Body Radiation Therapy (SBRT). When IMRT was applied, the most common (19/55 responders, 34.5%) selection of treatment volume consisted of the Gross Tumor Volume (GTV) + 0.5 cm margin to account for microscopic disease.ConclusionDespite the absence of definitive evidence-based recommendations, a possible consideration for ReRT in case of unresectable recurrent head and neck cancer was reported by over 80% of radiation oncologists taking part in the national survey.

Exploring the Role of Enzalutamide in Combination with Radiation Therapy: AnIn VitroStudy

Background/Aim: Androgen receptor plays a key role in prostate cancer development and is a causative agent of its radio-resistance. The present study investigated the potential radio-sensitizing effect of enzalutamide, a second-generation anti-androgen, in human prostate cancer cells. Materials and Methods: The radio-sensitizing effect of enzalutamide was assessed in the androgen-dependent LNCaP cells and the androgen-independent PC3 cells by clonogenic assay and γ-H2AX assay. Results: Enzalutamide-treated LNCaP cells showed a significant decrease of cell survival at all radiation doses tested. An increased number of γ-H2AX-positive nuclei was observed, suggesting a possible impairment of the DNA repair machinery. Conversely, enzalutamide did not exhibit a significant radio-sensitizing effect on PC3 cells. Conclusion: The combination of enzalutamide with ionizing radiation significantly improves radio-sensitivity of hormone-dependent LNCaP cells. Translated in the clinical practice, our results may help to find additional strategies to improve effectiveness of radiotherapy.

From chemotherapy to target therapies associated with radiation in the treatment of NSCLC: a durable marriage?

ABSTRACT Introduction: The integration between radiotherapy and drugs, from chemotherapy to recently available target therapies, continues to have a relevant role in the treatment of locally advanced and metastatic Non-small cell lung cancer (NSCLC). Aim of the present review is to evaluate the promising and emerging application of the best interaction between new drugs and new modalities of radiotherapy. Areas covered: We searched Medline, Google Scholar, PubMed, ProQuest Dissertation, and Theses databases for reports published in English. A study was included when it reported on cancer-related radiotherapy and included patients with NSCLC treated with chemo and/or target therapies. Review articles were excluded from the analysis. Expert commentary: Chemo-radiotherapy still represents the standard of choice in locally advanced NSCLC, while to date the addition of target therapies to chemo-radiotherapy did not demonstrate any robust advantage in this stage of disease. Considering the absence of randomized controlled trials, the role of target therapies in early stage adjuvant NSCLC is not yet recommended in clinical practice. On the contrary, in the setting of oligometastatic and oligoprogressive disease, new molecules demonstrated to be safe and effective, opening to a promising and emerging application of the best interaction between new drugs and new modalities of radiotherapy.