Is Locally Advanced Head-Neck Cancer One More Candidate for Accelerated Hypofractionation?

Abstract

Background/Aim: Hypofractionated accelerated radiotherapy (HypoAR) is widely applied for the treatment of early laryngeal cancer. Its role in locally advanced head-neck cancer (LA-HNC) is unexplored. Patients and Methods: We present results of a prospective trial on 124 patients with LA-HNC, treated with radio-chemotherapy with three different HypoAR fractionations . Results: Protraction of the overall treatment time due to oropharyngeal mucositis was enforced in 18/57 laryngeal, 6/19 nasopharyngeal, and 15/48 cancer patients with other tumors. Regarding late toxicities, laryngeal edema grade 3 was noted in 5/57 patients with laryngeal cancer, while severe dysphagia was noted in 4/124 and tracheoesophageal fistula formation in 1/124 patients. The complete response rates obtained were 73%, 84%, and 67% in patients with laryngeal, nasopharyngeal, and other tumors, respectively. The 3-year locoregional progression-free survival was 58%, 73%, and 55%, respectively. Conclusion: HypoAR chemoradiotherapy is feasible, with acceptable early and late radiotherapy toxicities, response rates and LPFS.The justified, to a certain point, phobia spread over the 1980s and 1990s regarding the severity of late complications from hypofractionation, promoted the switch of clinical trials towards hyperfractionated regimens. Hypofractionation was reduced to a clinical tool for overloaded radiotherapy departments or was used as a research tool by few heretics. In his 'lessons from complications' paper, G.H. Fletcher appeared convinced that hypofractionation produces unacceptable late toxicities in breast cancer (1). However, the whole breast's dose in the image case presented in the article was equal to a normalized biological total dose of 60Gy (5 fractions of 670 cGy). This dose would have produced similarly poor cosmetic results even if given with conventional fractionation. Today, hypofractionated and accelerated radiotherapy (HypoAR) is the standard of care for breast cancer patients (2, 3).The reconsideration of hypofractionation became feasible due to the technological advances in radiotherapy and, most importantly, the optimized calculation of the biological radiation dose (according to the linear-quadratic model formulas). Moreover, radiobiological analysis of large clinical data dissolved the long-lasting misconception that all tumors have a high α/β-value, challenging the supremacy of small doses per fraction. Today, HypoAR has gained the trust of Radiation Oncologists worldwide for the treatment of breast, prostate, and rectal cancer (2-6). The use of Stereotactic Body Radiotherapy SBRT, applying super-hypofractionated regimens, is gradually increasing, as the publications of favorable experiences are rapidly increasing (7).Regarding head-neck cancer, HypoAR is considered the standard of care for early laryngeal cancer (8). HypoAR is more effective than conventional radiotherapy (ConvRT) or even surgery for early laryngeal carcinomas (9). However, the overall world experience on HypoAR in locally advanced head-neck cancer (L...

Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head–Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy

“…One-hundred twenty-one patients with locally advanced HNSCC treated prospectively with RT/chemo-RT were analyzed. Details on the RT and chemotherapy schedules are reported in [ 10 ]. Briefly, patients were treated with accelerated hypofractionated RT delivering 20–22 fractions of 2.7 Gy to the tumor to an EQD2 (equivalent to 2 Gy fractionation dose) of 66–80 Gy.…”

Ultra-Hypofractionated Re-Irradiation with Anti-PD-1 Immunotherapy for Locoregionally Recurrent (after Radical Chemo-Radiotherapy) Non-Small Cell Lung Cancer

“…The RT dose delivered to the primary tumor was 49 Gy using an accelerated hypofractionated scheme, delivering 3.5 Gy/fraction for 14 fractions. This RT schedule, applying a simultaneous integrated dose technique (2.7 Gy/fraction to the nodal areas and 3.5 Gy/fraction to the primary tumor area), has been extensively tested for safety and efficacy by our group in combination with chemotherapy and is widely applied in our department [18][19][20]. This delivers an equivalent dose delivered in 2 Gy fractions (EQD2 or normalized total dose (NTD)), calculated for a lung α/β-ratio of 3 Gy, of 63.7 Gy within 18 days [21].…”

Precision medicine for risk prediction of oral complications of cancer therapy–The example of oral mucositis in patients receiving radiation therapy for cancers of the head and neck

“…Intensity modulated radiation therapy (IMRT) is currently preferred as it delivers more tumor-focused radiation thereby effectively reducing the level of cumulative radiation delivered to normal mucosal tissue when delivered in daily 2 Gy fractions. Since tumor response is dependent on both cumulative radiation dose and the time over which it is delivered, attempts at using higher daily radiation doses (daily fractions up to 3.5 Gy) in accelerated fractionation regimens have been suggested [ 20 , 21 ].…”