T. Vuong

The potential uses of high-dose-rate brachytherapy in patients with head and neck cancer

Brachytherapy has proven to be an extremely valuable method of treatment for head and neck cancer. The data supporting its application, however, is based on continuous low-dose-rate brachytherapy. To benefit from improved radiation protection, outpatient treatments, and increased patient tolerance of treatment set-up over that encountered in conventional low-dose-rate manually afterloaded brachytherapy, we implemented a high-dose-rate remote afterloading approach in selected patients with head and neck cancers. This treatment was utilized in two different roles in managing 29 patients. In its first role, it was used as the sole treatment in 13 patients with T1–2 NO malignancies. A total of ten treatments of 450–500 cGy each were delivered twice a day with a minimum of 5–6 h between treatments. With a median follow-up of 9 months, only 1 patient failed locally. In a second role, brachytherapy was applied in a post-operative adjuvant setting following wide local excision of tumors in patients who presented with recurrent disease (12 cases) or a second primary in the head and neck (4 cases). All patients had previously received external irradiation to the head and neck. Due to this previous course of irradiation, only eight treatments of 300 cGy each were delivered, for a total of 2400 cGy over a period of 4 days. However, with a follow-up of 2–16 months, only 3 patients remain disease-free.

Accelerated radiotherapy with simultaneous integrated boost fractionation and intensity-modulated radiotherapy for advanced head and neck cancer

Objective To determine the feasibility and toxicity profile of accelerated radiotherapy with a simultaneous integrated boost fractionation scheme with intensity-modulated radiotherapy (SIB-IMRT) with or without chemotherapy. Study Design And Setting Forty-nine patients with advanced head and neck cancer underwent SIB-IMRT. Concomitant chemotherapy was administered in 29 patients. Results Grade 3 acute toxicities included 55% mucositis, 20% odynophagia, 12% nausea, 18% hematologic, and 8% skin. There were no grade 4 toxicities or treatment-related deaths. With a median follow-up of 25 months, locoregional control was 83%, and overall survival was 80%. Of patients with grade 3 late toxicities, two patients (4% of the total) required a permanent percutaneous endoscopic gastrostomy tube, and osteonecrosis occurred in one patient (2% of the total). Conclusions SIB-IMRT is a feasible technique that shortens the overall treatment time in the radical treatment of patients with advanced head and neck cancer while maintaining acceptable rates of acute toxicity in this study. Although the results are promising, this approach should be considered only in the setting of a clinical trial.

Effects of dna-dependent protein kinase inhibition by NU7026 on dna repair and cell survival in irradiated gastric cancer cell line N87

UNLABELLEDnRepair of radiation-induced dna double-strand breaks is a key mechanism in cancer cell radio-resistance. The synthesized compound NU7026 specifically inhibits dna-dependent protein kinase (dna-pk) within the non-homologous end-joining repair mechanism. Earlier studies demonstrated increased radiosensitivity in dna-pk deficient cells compared with wild-type cells. In chronic leukemia cells, NU7026 appears to enhance the cytotoxic effect of chlorambucil. The radio-modifying effects of NU7026 on cell survival, cell cycle, apoptosis, and dna double-strand break repair have yet to be studied in gastric cancer cells.nnnMETHODSnThe gastric cancer cell line N87 was treated with 0 Gy or 4 Gy in the presence of NU7026 at a dose range of 0-20 μmol/L. Clonogenic assays were used to assess cell survival after treatment. Cell-cycle distribution was analyzed using propidium iodide with fluorescence-activated cell sorting. Apoptosis was detected using annexin-V and propidium iodide with fluorescence-activated cell sorting. The γH2AX assay was used to measure dna double-strand breaks.nnnRESULTSnStatistically significant increases in G2/M arrest were observed in N87 cells treated with radiation and NU7026 compared with those treated with radiation alone (p = 0.0004). Combined treatment also led to an increase in apoptosis (p = 0.01). At 24 hours, the γH2AX analysis revealed more dna double-strand breaks in N87 cells treated with radiation and NU7026 than in those treated with radiation alone (p = 0.04). Clonogenic assays demonstrated declining cell survival as both the radiation and the NU7026 dose increased. The dose enhancement factor at 0.1 survival fraction was 1.28 when N87 cells were treated with 4 Gy radiation and 5 μmol/L NU7026.nnnCONCLUSIONSnIn gastric cancer cells, NU7026 appears to enhance the cytotoxic effect of irradiation as assessed by clonogenic assays. This increased cytotoxicity might be the result of an increase in dna double-strand breaks resulting in G2/M cell arrest and possibly higher levels of apoptosis.

The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

PURPOSEnAcute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT).nnnMETHODS AND MATERIALSnFifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receive the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT.nnnRESULTSnAt the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078).nnnCONCLUSIONSnThis study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.

CT-based adaptive high-dose-rate endorectal brachytherapy in the preoperative treatment of locally advanced rectal cancer: Technical and practical aspects

PURPOSEnDuring the last decade due to the availability of a CT scan in the brachytherapy suite, high-dose-rate endorectal brachytherapy (HDREBT) has evolved as a CT-based daily adaptive treatment. An update of the technical and practical aspects of HDREBT is provided.nnnMETHODS AND MATERIALSnDescription of technical and practical aspects of HDREBT focused on the preoperative treatment of locally advanced rectal cancer. During preoperative HDREBT, 26xa0Gy is delivered in four daily applications of 6.5xa0Gy prescribed to the 100% isodose, covering the clinical target volume. Daily CT scans are obtained and used for plan optimization, leaving patient positioning unchanged between CT scan and treatment delivery.nnnRESULTSnAll steps of HDREBT treatment procedure are discussed in detail: flexible proctosigmoidoscopy and clipping; patient setup; applicator placement; target delineation; treatment planning and delivery; and patient care. Afterward, treatment results are reviewed.nnnCONCLUSIONSnCT-based adaptive preoperative HDREBT is a practical and feasible therapy for locally advanced rectal cancer, offering excellent local control with a favorable toxicity profile.