• 9/6/2006
  • Australia, Canada, Finland
  • Rischen et al; Lau et al; Luukkaa et al
  • TherapeuticsDaily.com

Reports from Australia, Canada and Finland highlight recent research in head & neck cancer.

Study 1:
The risk of locoregional failure (LRF) in head and neck cancer patients receiving a nontirapazamine-containing chemoradiotherapy regimen could be related to tumor hypoxia.

Researchers in Australia conducted a study “to determine the association between tumor hypoxia, treatment regimen, and LRF in patients with stage III or IV squamous cell carcinoma of the head and neck randomly assigned to radiotherapy (70 Gy in 35 fractions over 7 weeks) plus either tirapazamine and cisplatin in weeks 1, 4, and 7 and tirapazamine alone in weeks 2 and 3 (TPZ/CIS) or cisplatin and infusional fluorouracil during weeks 6 and 7 (chemoboost).”

“Forty-five patients were enrolled onto a hypoxic imaging substudy of a larger randomized trial,” explained D. Rischin and colleagues, Peter MacCallum Cancer Center. “Pretreatment and midtreatment [F-18]-fluoromisonidazole positron emission tomography scans (FMISO-PET) were performed 2 hours after tracer administration, with qualitative scoring of uptake in both primary tumors and nodes. Thirty-two patients (71%) had detectable hypoxia in either or both primary and nodal disease.”

“In patients who received chemoboost, 1 of 10 patients without hypoxia had LBF compared with 8 of 13 patients with hypoxia; the risk of LRF was significantly higher in hypoxic patients (exact log-rank, p=.038; hazard ratio [HR]=7.1). By contrast, in patients who received the TPZ/CIS regimen, only 1 of 19 patients with hypoxic tumors had LRF; risk of LRF was significantly higher in chemoboost patients (p=.001; HR=15). Similarly, looking at the primary site alone, in patients with hypoxic primaries, 0 of 8 patients treated with TPZ/CIS experienced failure locally compared with 6 of 9 patients treated with chemoboost (p=011; HR=0).”

The researchers concluded, “Hypoxia on FMISO-PET imaging, in patients receiving a nontirapazamine-containing chemoradiotherapy regimen, is associated with a high risk of LRF. Our data provide the first clinical evidence to support the experimental observation that tirapazamine acts by specifically targeting hypoxic tumor cells.”

Source:
Rischin and colleagues published their study in the Journal of Clinical Oncology (Prognostic significance of [F-18]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: A substudy of Trans-Tasman Radiation O. J Clin Oncol, 2006;24(13):2098-2104).

For additional information, contact D. Rischin, Peter MacCallum Cancer Center, Division Hematology & Med Oncology, Center Molecular Imaging, Division Radiation Oncology, Locked Bag 1, A Beckett St., Melbourne, Vic 8006, Australia.

Study 2:
Head and neck squamous cell carcinoma (SCCHN) could be treated by low-dose cisplatin and three-dimensional conformal radiotherapy.

“Our center sought to implement a simple chemoradiotherapy schedule for patients with locally advanced SCCHN with minimal toxicity to achieve rates of overall survival comparable to other schedules. The chemoradiotherapy schedule consisted of daily radiation to 70 Gy over 7 weeks with concurrent cisplatin 20 mg/m2 during days 1 to 4 of weeks 1 and 5,” investigators in Canada reported.

“Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group (RTOG) and common toxicity criteria (CTC) grading,” explained H. Lau and colleagues, Tom Baker Cancer Clinic. “The overall, disease-specific, and locoregional recurrence-free survival were calculated using the STATA statistics package. Possible factors influencing these endpoints were analyzed.

“Fifty-seven patients were treated, and 56 patients were evaluable for follow-up. Median follow-up of alive patients was 16.1 months. There was an 82% complete response rate to chemoradiotherapy. The 2-year Kaplan-Meier overall, disease-specific, and locoregional recurrence-free survival rates were 62%, 67%, and 63%. Acute grade 3 and 4 radiation toxicity was noted in 61% and 2%, respectively. Grade 3 or 4 hematologic toxicity was noted in 7% of patients.”

The researchers concluded, “Factors influencing overall survival included: Karnofsky performance status, receiving more than 50% of planned chemotherapy, age, and initial hemoglobin level. This regimen is tolerable and achieves overall survival and locoregional control rates comparable to other chemoradiotherapy schedules.”

Source:
Lau and colleagues published their study in Head and Neck – Journal for the Sciences and Specialties of the Head and Neck (Concomitant low-dose cisplatin and three-dimensional conformal radiotherapy for locally advanced squamous cell carcinoma of the head and neck: Analysis of survival and toxicity. Head Neck, 2006;28(3):189-196).

For additional information, contact H. Lau, Tom Baker Cancer Clinic, Dept. Radiation Oncology, 1331 29 St. NW, Calgary, AB T2N 4N2, Canada.

Study 3:
Aggressiveness of squamous cell carcinoma of the head and neck (HNSCC) could be linked to a high level of matrix metalloproteinase-13 (MMP-13) expression.

According to recent research published in the Head and Neck – Journal for the Sciences and Specialties of the Head and Neck, “HNSCC is a common cancer type. The ability for curative treatment with surgery and radiotherapy (RT) is usually highly dependent on tumor stage at the time of diagnosis. The purpose of this study was to determine whether the expression of a cancer-specific proteinase, collagenase-3 (MMP-13), is associated with survival parameters in patients with HNSCC.”

“We studied MMP-13 expression in tumors of 81 patients with stage I-IV HNSCC treated with surgery alone or in combination with radiotherapy,” explained M. Luukkaa and colleagues, Turku University Hospital. “We found a subgroup of patients with high MMP-13 expression level in their tumors (greater than or equal to90% MMP-13-positive tumor cells) associated with unfavorable prognosis (median overall survival [OS], 11.8 vs 19.6 months, p=.032).”

“In addition, the median disease-specific survival (DSS) time was markedly reduced in this subgroup (13.8 months vs 40.7 months, p=.062). When the subgroup of patients treated with a curative intent was studied, the same association was found in OS (13.8 vs 24.6 months, p=.023) and DSS (p=.004). In addition, there was a trend for association between greater than or equal to90% MMP-13 positivity and a recurrent tumor (p=.078) in curatively treated patients. The short survival time associated with high MMP-13 expression levels could not be predicted by tumor size or local lymph node invasion.”

The researchers concluded, “These results show that a high MMP-13 expression level is associated with aggressiveness of HNSCC and may have prognostic value in patient evaluation.”

Source:
Luukkaa and colleagues published their study in Head and Neck – Journal for the Sciences and Specialties of the Head and Neck (Association between high collagenase-3 expression levels and poor prognosis in patients with head and neck cancer. Head Neck, 2006;28(3):225-234).

For additional information, contact M. Luukkaa, Turku University Hospital, Dept. Radiotherapy & Oncology, POB 52, FIN-20521 Turku, Finland.