Combined modality treatment with full-dose chemotherapy and concomitant boost radiotherapy for advanced head and neck carcinoma

The purpose of this study was to evaluate the feasibility and efficacy of a treatment concept combining three cycles of full-dose chemotherapy (CT) with concomitant accelerated uninterrupted radiotherapy (RT). Twenty-three patients (median age: 54years, range: 35-70) with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were included. The primary tumor involved the hypopharynx (n=7), base of the tongue (n=10), nasopharynx (n=2) or upper esophagus (n=1) or its location was unknown (n=3). Treatment consisted of three cycles of chemotherapy (cisplatin 100mg/m2 on day 1; 5-FU 1,000mg/m2 per day for 5days as a continuous infusion, preceded by amifostine 910mg/m2), repeated every 3weeks. Uninterrupted concomitant boost-accelerated RT (total dose of 70Gy in 6weeks) started together on day 1 of the second cycle. All but two patients received the full course of RT. Eighteen patients achieved complete remission (78%). At a median follow-up of 45months the overall survival was 56% (95% c.i. 32-79%) and the loco-regional control 71% (95% c.i. 52-91%). Toxicity involved reversible renal insufficiency of ≥ grade II in 9 patients (39%) and neutropenic fever in 9 patients (39%). All patients suffered from moderate to severe mucositis (grade II/III), and 19 patients presented cutaneous toxicity grade III. Concomitant boost-accelerated RT combined with concurrent full-dose cisplatin/5-FU chemotherapy and amifostine is feasible with manageable, although substantial, toxicity. The overall survival of 4years is promising. Newer regimens causing less acute mucosal and skin toxicity are neede

The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications

Epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptors. Its stimulation by endogenous ligands, EGF or transforming growth factor-alpha (TGF-α) results in activation of intracellular tyrosine kinase, therefore, cell cycle progression. High levels of EGFR expression are correlated with poor prognosis and resistance to radiation therapy in a variety of cancers, mostly in squamous-cell carcinoma of the head and neck (SCCHN). Blocking the EGFR by a monoclonal antibody results in inhibition of the stimulation of the receptor, therefore, in inhibition of cell proliferation, enhanced apoptosis, and reduced angiogenesis, invasiveness and metastases. The EGFR is a prime target for new anticancer therapy in SCCHN, and other agents in development include small molecular tyrosine kinase inhibitors and antisense therapies

Long-term Outcome and Late Side Effects in Endometrial Cancer Patients Treated with Surgery and Postoperative Radiation Therapy

Background: We retrospectively reviewed the long-term outcome and late side effects of endometrial cancer (EC) patients treated with different techniques of postoperative radiotherapy (PORT). Methods: Between 1999 and 2012, 237 patients with EC were treated with PORT. Two-dimensional external beam radiotherapy (2D-EBRT) was used in 69 patients (30%), three-dimensional EBRT (3D-EBRT) in 51 (21%), and intensity-modulated RT (IMRT) with helical Tomotherapy in 47 (20%). All patients received a vaginal brachytherapy (VB) boost. Seventy patients (29%) received VB alone. Results: After a median of 68months (range, 6-154) of follow-up, overall survival was 75% [95% confidence interval (CI), 69-81], disease-free survival was 72% (95% CI, 66-78), cancer-specific survival was 85% (95% CI, 80-89), and locoregional control was 86% (95% CI, 81-91). The 5-year estimates of grade 3 or more toxicity and second cancer rates were 0 and 7% (95% CI, 1-13) for VB alone, 6% (95% CI, 1-11) and 0% for IMRT+VB, 9% (95% CI, 1-17) and 5% (95% CI, 1-9) for 3D-EBRT+VB, and 22% (95% CI, 12-32) and 12% (95% CI, 4-20) for 2D-EBRT+VB (P=0.002 and P=0.01), respectively. Conclusions: Pelvic EBRT should be tailored to patients with high-risk EC because the severe late toxicity observed might outweigh the benefits. When EBRT is prescribed for EC, IMRT should be considered, because it was associated with a significant reduction of severe late side effects

Decrease in Hemoglobin Levels Following Surgery Influences the Outcome in Head and Neck Cancer Patients Treated with Accelerated Postoperative Radiotherapy

Aim: To assess the influence of hemoglobin (Hb) levels in locally advanced head and neck cancer (LAHNC) patients treated with surgery and postoperative radiotherapy (PORT). Material and Methods: Pre- and postoperative Hb levels were collected in 79 patients treated with surgery followed by accelerated PORT for LAHNC. Median follow-up was 52months (range 12-95months). Results and Discussion: Four-year overall survival (OS) rate was 51%. Neither pre- nor postoperative Hb level (<120 or 130g/l in women or men, respectively) influenced the outcome. However, when Hb decrease between pre- and postoperative Hb values was taken into account, 4-year OS was significantly higher in patients with Hb difference less than 38g/l (quartile value) compared with those with Hb decrease 38g/l or more (61% versus 16%, P=0.008). Conclusion: Decrease in Hb level by more than 38g/l after surgery secondary to blood loss influences the outcome when postoperative RT is indicate

Letrozole sensitizes breast cancer cells to ionizing radiation

INTRODUCTION: Radiotherapy (RT) is considered a standard treatment option after surgery for breast cancer. Letrozole, an aromatase inhibitor, is being evaluated in the adjuvant setting. We determined the effects of the combination of RT and letrozole in the aromatase-expressing breast tumour cell line MCF-7CA, stably transfected with the CYP19 gene. METHODS: Irradiations were performed using a cobalt-60 source with doses ranging from 0 to 4 Gy. Cells were incubated with androstenedione in the presence or absence of letrozole. Effects of treatment were evaluated using clonogenic assays, tetrazolium salt colorimetric (MTT) assays, and cell number determinations. Cell-cycle analyses were conducted using flow cytometry. RESULTS: The survival fraction at 2 Gy was 0.66 for RT alone and was 0.44 for RT plus letrozole (P = 0.02). Growth of MCF-7CA cells as measured by the cell number 6 days after radiotherapy (2 and 4 Gy) was decreased by 76% in those cells treated additionally with letrozole (0.7 μM) compared with those receiving radiotherapy alone (P = 0.009). Growth inhibition, assessed either by cell number (P = 0.009) or by the MTT assay (P = 0.02), was increased after 12 days of the combination treatment. Compared with radiation alone, the combination of radiation and letrozole produced a significant decrease in radiation-induced G(2 )phase arrest and a decrease of cells in the S phase, with cell redistribution in the G(1 )phase. CONCLUSIONS: These radiobiological results may form the basis for concurrent use of letrozole and radiation as postsurgical adjuvant therapy for breast cancer

Feasibility and Efficacy of Accelerated Weekly Concomitant Boost Postoperative Radiation Therapy Combined with Concomitant Chemotherapy in Patients with Locally Advanced Head and Neck Cancer

Background: The aim of this study was to assess feasibility and efficacy of weekly concomitant boost accelerated postoperative radiation therapy (PORT) with concomitant chemotherapy (CT) in patients with locally advanced head and neck cancer (LAHNC). Methods and Materials: Conformal or intensity-modulated 66-Gy RT was performed in 5.5weeks in 40 patients. Cisplatin was given at days 1, 22, and 43. Median follow-up was 36months. Results and Discussion: Grade 3 mucositis, dysphagia, and erythema was observed in ten (25%), nine (23%), and six (13%) patients, respectively. Grade 3 or more anemia was observed in two (6%) patients, and leukopenia in five (13%) patients. No grade 3 or 4 thrombocytopenia was observed. Grade 3 nephrotoxicity was observed in one patient (3%). No treatment-related mortality was observed. Grade 2 or more xerostomia and edema were observed in ten (25%) and one (3%) patient, respectively. Locoregional relapse occurred in eight patients, and seven patients developed distant metastases. Median time to locoregional relapse was 6months. Three-year overall, disease-free survival, and locoregional control rates were 63%, 62%, and 81%, respectively. Multivariate analysis revealed that the only prognostic factor was nodal status. Conclusion: Reducing overall treatment time using accelerated PORT/CT by weekly concomitant boost (six fractions per week) combined with concomitant cisplatin CT is easily feasible with acceptable morbidit

Re-irradiation of recurrent vertebral metastasis after two previous spinal cord irradiation: A case report

BackgroundManagement of a recurrent vertebral metastasis in a situation of previously irradiated spinal cord is a challenging clinical dilemma.Case presentationWe report a first case of second retreatment of a spinal metastasis initially irradiated with standard radiotherapy and stereotactic body radiation therapy (SBRT), who subsequently progressed with imaging-confirmed local tumor progression at the same level. After a third course of irradiation with SBRT, a complete response was achieved. After 8 months of follow-up, the patients remain free of local recurrence.ConclusionA third course of vertebral irradiation for a recurrent vertebral metastasis failing to two previous irradiations, in this particular case, have shown the feasibility and efficacy of the technique as a salvage treatment option. This approach could be used in a selected group of patient if an adequate dose is delivered to the target while observing critical tissue tolerance limits

Primary Hepatic Lymphoma: A Retrospective, Multicenter Rare Cancer Network Study.

Primary hepatic lymphoma (PHL) is a rare malignancy. We aimed to assess the clinical profile, outcome and prognostic factors in PHL through the Rare Cancer Network (RCN). A retrospective analysis of 41 patients was performed. Median age was 62 years (range, 23-86 years) with a male-to-female ratio of 1.9:1.0. Abdominal pain or discomfort was the most common presenting symptom. Regarding B-symptoms, 19.5% of patients had fever, 17.1% weight loss, and 9.8% night sweats. The most common radiological presentation was multiple lesions. Liver function tests were elevated in 56.1% of patients. The most common histopathological diagnosis was diffuse large B-cell lymphoma (65.9%). Most of the patients received Chop-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens; 4 patients received radiotherapy (dose range, 30.6-40.0 Gy). Median survival was 163 months, and 5- and 10-year overall survival rates were 77 and 59%, respectively. The 5- and 10-year disease-free and lymphoma-specific survival rates were 69, 56, 87 and 70%, respectively. Multivariate analysis revealed that fever, weight loss, and normal hemoglobin level were the independent factors influencing the outcome. In this retrospective multicenter RCN study, patients with PHL had a relatively better prognosis than that reported elsewhere. Multicenter prospective studies are still warranted to establish treatment guidelines, outcome, and prognostic factors

Primary breast lymphoma: patient profile, outcome and prognostic factors. A multicentre rare cancer network study

Background: To asses the clinical profile, treatment outcome and prognostic factors in primary breast lymphoma (PBL). Methods: Between 1970 and 2000, 84 consecutive patients with PBL were treated in 20 institutions of the Rare Cancer Network. Forty-six patients had Ann Arbor stage IE, 33 stage IIE, 1 stage IIIE, 2 stage IVE and 2 an unknown stage. Twenty-one underwent a mastectomy, 39 conservative surgery and 23 biopsy; 51 received radiotherapy (RT) with (n = 37) or without (n = 14) chemotherapy. Median RT dose was 40 Gy (range 12-55 Gy). Results: Ten (12%) patients progressed locally and 43 (55%) had a systemic relapse. Central nervous system (CNS) was the site of relapse in 12 (14%) cases. The 5-yr overall survival, lymphoma-specific survival, disease-free survival and local control rates were 53%, 59%, 41% and 87% respectively. In the univariate analyses, favorable prognostic factors were early stage, conservative surgery, RT administration and combined modality treatment. Multivariate analysis showed that early stage and the use of RT were favorable prognostic factors. Conclusion: The outcome of PBL is fair. Local control is excellent with RT or combined modality treatment but systemic relapses, including that in the CNS, occurs frequentl