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.

toxicity-related events that patients frequently inquire about in our multidisciplinary clinic: the need for urgent tracheotomy, the likelihood of PEG tube-dependence, hospitalization, operative repair or debride- ment of soft tissue complications, and hemorrhage. We determined the time to these events to assist clinicians with anticipating when such toxicities may occur and allowing them to counsel patients accordingly. Lastly, we examined predictors for toxicity including those frequently cited in tumor-board discussions such as the placement of a vascular- ized fl ap prior to reRT, the interval between courses of RT, sequencing of chemotherapy, and radiation dose to normal tissues.

Outcome assessment

At the completion of reRT, patients were monitored every 1 – 2 weeks until resolution or stabilization of acute side e ff ects and every 1 – 2 months thereafter. The diagnosis of recurrence after reRT was con fi rmed with biopsy for most patients (n = 23), radiographic imaging only (n = 10), or clinical examination only (n = 2). In all cases, detailed information regarding the sites of recurrence in re- lationship to the irradiated area was obtained.

Toxicity assessment

Materials and methods

Toxicity was retrospectively graded with the Common Terminology Criteria for Adverse Events (CTCAE) version 4. To minimize bias in- troduced by retrospective toxicity grading, a composite toxicity end- point termed “ serious toxicity ” was de fi ned similar to that of Sulman et al. [9] yet with a more inclusive de fi nition. Patients were considered to have a ‘ serious toxicity ” if they had at least one of the following: major hemorrhage from the head and neck area (either mucosal or cutaneous) requiring hospitalization, hospitalization during RT, tra- cheotomy after the start of reRT, soft tissue complication requiring operative debridement or reconstruction (included fi stulas and osteor- adionecrosis requiring surgical debridement), or other grade ≥ 4 toxi- city. Hospitalizations during induction chemotherapy were not in- cluded in the toxicity endpoint as the primary focus was on toxicity during and after reRT. PEG tube at last follow-up was evaluated as a time varying cov- ariate. The association with toxicity was evaluated using single and multivariable logistic regression models and the odds ratio, 95% con- fi dence intervals and p-values were reported. The date of composite toxicity was de fi ned as the earliest date of the individual composite toxicity events including date of hemorrhage, urgent tracheotomy, acute hospitalization, reported necrosis, or surgical repair of a soft tissue toxicity. The time from reRT start date to composite toxicity date was evaluated as a time to event analysis using Kaplan-Meier. For time to composite toxicity analysis patients were censored at date of last evaluation for LR. Analyses were performed using Stata (version 13.0, Stata Corp LP, College Station, TX) and SAS (version 9.3, SAS Institute Inc., Cary, NC). Statistical analysis Table 1 shows patient characteristics and treatment details for the initial radiation course and the most recent reRT course. Most patients received an initial de fi nitive course of RT with conformal or IMRT techniques at outside institutions to a median total dose of 70 Gy using conventional fractionation. The median interval between radiation courses was 2.5 years (range, 0.2 – 26.4 years) with most patients re- ceiving reRT for recurrence (n = 49, 65%) rather than a second pri- mary (n = 26, 35%). Most patients (88%) received concurrent pla- tinum-based chemotherapy with reRT, including 12 patients (16%) who received induction chemotherapy prior to the concurrent phase of therapy. The use of surgical salvage varied signi fi cantly depending on the site of disease (p < 0.001) and was more likely to be used for an isolated neck recurrence or oral cavity recurrence/s primary compared with the oropharynx ( Table 2 ). De fi nitive reRT was more likely for oropharynx or nasopharynx sites. For larynx/hypopharynx, reRT was de fi nitive in 52% (12 of 23) cases. Results Treatment characteristics

Patients and treatment

We reviewed the medical records of seventy- fi ve consecutive pa- tients that received re-irradiation with IMRT for recurrent or second primary squamous cell carcinoma of the head and neck from 08/2004 (when IMRT was fi rst used in the clinic) to 02/2013. All patients had received a prior course of de fi nitive or postoperative radiation therapy (RT) either at our institution or at an outside institution. Patients were considered to have a second primary tumor if the tumor was diag- nosed >5 years after the initial cancer and/or occurred in an anato- mically-distinct region. ReRT was o ff ered to select patients after mul- tidisciplinary evaluation by the radiation oncologist, otolaryngologist/ head and neck surgeon, and medical oncologist. Patients deemed to have resectable disease were o ff ered salvage surgery. Post-operative reRT was o ff ered in select cases with high-risk features such as close or positive margins and extracapsular spread. Patients were o ff ered de fi - nitive reRT without surgical salvage if they had unresectable disease or surgery was declined by the patient. Two patients were excluded from the analysis because they stopped reRT due to tumor progression (8 Gray [Gy] into treatment) and transitioned to hospice (20 Gy into treatment) and did not have treatment-related side e ff ects at the time of radiation discontinuation. For patients treated with an initial course of radiation at an outside institution, the graphic plan or simulation fi lms were obtained where possible to con fi rm dose to the target volumes and normal tissues. In general, patients who completed radiation within 6 months of recur- rence were not candidates for reRT unless, after review of the prior radiation plan, the recurrence was considered to be a “ marginal miss ” and predominantly out of the highest-dose area suggesting that the recurrence did not necessarily represent radioresistant disease; there were 4 such cases with interval of re-irradiation <6 months (range 2.4 – 5.1 months). RT was delivered with IMRT and planned using Eclipse planning software (Varian Medical Systems, Palo Alto, CA). The radiation target volume typically included gross disease (GTV) with a 5 mm planning target volume (PTV) margin. Postoperative clinical target volumes (CTV) included the postoperative bed or the area of highest concern after discussion with the surgeon and pathology review, with a 1 – 1.5 cm margin for subclinical spread and a 5 mm (PTV) expansion. Elective neck irradiation was not routinely used, but was considered when there was a high-risk of subclinical spread to the neck in an area that was not included in the target volume during the initial course of radiation. The primary avoidance structure was the spinal cord with a limit of 10 – 12 Gy at the time of reRT. Similar limitations were used for the brain stem dose. In general, the prescription dose was 60 Gy in 30 fractions (range, 59.4 – 70 Gy). Concurrent chemotherapy was given in most cases of reRT. Induction chemotherapy was given at the discretion of the treating physicians, but in general was considered for patients with T4 tumors or N3 nodal disease.

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