2018-19 Section 7-Neoplastic and Inflammatory Diseases of the Head and Neck eBook

Oral Oncology 73 (2017) 160–165

D.N. Margalit et al.

Fig. 1. Kaplan-Meier curve for time to serious toxicity from the start of reirradiation by timing of re-irradiation (postoperative versus de fi nitive).

WŽƐƚŽƉĞƌĂƟǀĞ reRT

eĮŶŝƟǀe reRT

ProďĂďŝůŝty

Tŝme to toxŝcŝty

We sought to determine if there was indeed decreased toxicity after reRT when patients had placement of free- fl aps or pedicled fl aps. Amongst patients that were treated with surgery, we did not fi nd an obvious reduction of serious toxicity associated with fl ap reconstruction compared with surgical patients that did not have such reconstructions (53.9% vs. 46.2%; p = 0.64). These results must be interpreted with caution as the extent of resection may have been much greater in the free fl ap cases and along with this comes a greater risk of fi stula and wound complications requiring re-operation. Only one patient that developed a hemorrhage was previously treated with surgery and ad- juvant reRT, precluding analysis of the relationship between re- construction and hemorrhage. Interestingly, we did not fi nd an association between the interval between prior RT and reRT and subsequent toxicity after reRT. This agrees with a previous study showing that interval from prior radiation had no association with risk of serious toxicity (HR 0.99, p0.66) when dichotomized to ≤ 3 years compared with >3 years [8] . While radio- biological modeling accounts for time since radiation as a protective a ff ect for allowing repair of sublethal damage in normal tissue, this has not been de fi nitively shown in the clinical context. Our data suggest that interval between treatment cannot be used as a reliable predictor of reduced toxicity after head and neck reRT. Prior work showed that in the setting of reRT, concurrent che- motherapy increases the rate of toxicity compared with RT alone [8] . Since so few of our patients received RT alone, we were not able to do this comparison yet we did not see a di ff erence in toxicity based on whether chemotherapy was given as induction versus concurrent che- moradiation. Radiation planning is important in limiting dose to normal struc- tures to minimize the toxicity of treatment. While it did not achieve statistical signi fi cance, dose to the larynx was higher among patients that received a tracheotomy (median 48.0 vs. 40.1 Gy; p = 0.18). Radiation planning should include careful avoidance of the larynx where at all possible to minimize the risk of respiratory compromise. This can be challenging or even impossible when the tumor is near the larynx or when dose entry/exit is limited due to need to avoid the spinal cord. While treatment-related toxicities are high, this must be balanced with the functional compromise that is typically caused by a local re- currence. For example, patients with a local recurrence were more likely to be PEG tube-dependent at last follow-up than patients without a local recurrence (86% vs. 53% PEG tube-use, p = 0.001). Yet the risk of PEG tube-dependence among local disease-free patients is still > 50%. This result is consistent with prior studies of reRT with IMRT that include a population treated mostly with chemoradiation [3,6] .

Table 5 Association of toxicity with reconstruction for postoperative patients (n = 37). Serious toxicity de fi ned as at least one of the following: hemorrhage from the head and neck (either mucosal or cutaneous), hospitalization during radiation therapy, tracheotomy after the start of reirradiation, soft tissue complication requiring surgical debridement or reconstruction, or other grade ≥ 4 toxicity.

Variable

Serious toxicity = no (n = 24)

Serious toxicity = yes (n = 13)

OR (95% CI) P-value

Free/pedicled fl ap No (n = 19) 13 (54.2%)

6 (46.2%)

1.0 (Reference) 1.38 (0.36, 5.34)

N/A

Yes (18)

11 (45.8%)

7 (53.9%)

0.64

OR = odds ratio, CI = con fi dence interval.

Discussion

Patients that receive reRT with IMRT for SCCHN should be coun- seled on the high-risk of PEG tube-dependence, tracheotomy, hospita- lization, and need for operative interventions, in addition to the po- tentially fatal risk of hemorrhage. Many of these life-threatening complications occur months to years after reRT, making follow-up es- sential for identifying deterioration in swallowing or respiratory status. We found that hemorrhage was uncommon amongst patients with one prior course of radiation who were also disease-free, occurring in one such patient out of the 75-patient cohort. This is consistent with prior studies of head and neck reRT that estimated the rate of carotid blow-out to be approximately 1.5 – 4.5% amongst a diverse group of studies with various fractionation regimens and uses of chemotherapy [11] . Out of the 4 fatal hemorrhages, only one patient was disease-free with a total of 2 courses of radiation; the other disease-free patient had a total of 3 courses of radiation. In this series, there was a 5% crude rate of fatal hemorrhage and 2.7% crude rate of fatal hemorrhage in the absence of disease. The use of postoperative rather than de fi nitive reRT was associated with lower odds of serious toxicity despite similar total dose (median 60Gy). This is consistent with a prior study [8] and may represent the fact that operable tumors are potentially less advanced and in fi ltrative or free from large vessel encasement. Patients that undergo surgery prior to reRT may not be at risk of certain toxicities such as the need for urgent tracheotomy or aspiration pneumonia requiring hospitalization if, for example, they had a laryngectomy. Additionally, patients may bene fi t from having new tissue brought into the previously irradiated fi eld.

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