Clock in radiation oncology clinics: cost-free modality to alleviate treatment-related toxicity

Figures & data

Figure 1. Threshold-sigmoid dose response curve. A) High doses of ionizing radiation result in increased probability of tumor control that is often accompanied by an apparent increase in late complications as a result of inevitable irradiation of the surrounding healthy tissue. B) Low normal tissue complication risk in chronomodulated treatment. The therapeutic index is the difference between cure and toxicity. The larger the therapeutic ratio, the more likely the treatment is safe and effective.

Table 1. Timing – it’s the secret ingredient of RT treatment

Tumor site	Number of patients	Clinical characteristics of patients		Radiotherapy-delivery times	Outcome
		Gender	Age (median [range], years)
HNSCC^[Citation40]	212 patients	33women 144 men	[<35–70]	Morning (08:00–11:00) Evening (15:00–18:00	The morning arm had a reduction in therapy-related complications.
HNSCC^[41]	205 patients	49 women 167 men	60.0 [40–>70]	Morning (08:00–10:00) Afternoon(16:00–18:00)	For patients treated with a dose of 66 Gy or higher, those treated mornings had a significantly lower incidence of grade III/IV mucositis and longer intervals to the development of severe mucositis (median, >7.9 vs. 5.6 weeks).
HNSCC^[42]	190 patients	42 women 148 men	61.8 [<55–≥70]	Morning (08:30–<11:30) Early afternoon (11:30–15:00) Late afternoon (15:00–16:30)	Early afternoon group had a significantly higher prevalence of grade III/IV oral mucositis.
HNSCC^[44]	617 patients	140 women 477 men	62 [20–91]	DARK* LIGHT*	Higher acute toxicity occurred with radiation therapy in DARK.
Cervical Carcinoma^[46]	229 patients	229 women	49.3	Morning (08:00–10:00) Evening (18:00–20:00)	GI toxicity was less prevalent for those treated in the evening, which was graded in terms of diarrhea.
Cervical cancer^[47]	67 patients	67 women		Morning (09:00–11:00) Evening (21:00–23:00)	Higher incidence of severe hematological toxicity in the evening group.
Prostate adenocarcinoma^[48]	409 patients	409 men	73.5 [50–91]	Day time (before 17:00) Evening (after 17:00)	Acute GI and GU toxicities were noted more often in patients who were given evening treatment appointments in association with worse freedom from grade ≥ 2 late gastrointestinal toxicities.
Prostate cancer^[49]	168 patients	168 men	68 [53–86]	Morning (08:30–10:30) Noon (10:31–14:30) Late afternoon (14:31–16:30)	Morning treatment ameliorates PBT-related LUTS.
Breast cancer^[50]	395 patients	395 women	46.5 [22–81]	Morning (prior to 10:00) Afternoon (after 15:00)	The afternoon group had significantly worse acute toxicity.
Breast cancer^[54]	879 patients (obtained from two cohorts)	879 women	59.5 (across two cohorts)	Morning and afternoon	The morning group had a statistically significantly higher incidence of late toxicities.
NSCLC with brain metastasis^[15]	97 patients		62	Morning (10:00–12:30) Afternoon (12:30–15:00)	The morning group had significantly greater local control and fewer CNS-related deaths.
Lung cancer, nasopharyngeal carcinoma, cervical cancer, and esophageal cancer^[66]	121 patients	46 women 75 men	52.5 [28–79]	Morning at 9:00 Evening at 21:00	The morning group had significantly higher incidence of radiotherapy-related toxicity.

* The time of year to the spring equinox from the autumnal equinox was categorized as DARK and the other half as LIGHT

HNSCC, head and neck squamous cell carcinoma; GI, gastrointestinal; GU, genitourinary; PBT, proton beam therapy; LUTS, lower urinary tract symptoms; NSCLC, non-small cell lung cancer; CNS, central nervous system

Jiang D, Mierzwa ML, Huth B, Xie C, Barrett WL, Redmond KP, Forster N. 2015. Does time of daily treatment matter in radiation therapy for head and neck cancer? Int J Radiat Oncol Biol Phys. 93(3):E348. doi:10.1016/j.ijrobp.2015.07.1434.

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