Table 1.
Treatment Recommendations By Subsite During the Pandemic
| Subsite a | Treatment Recommendations During Pandemic | Rationale and Guiding Principles |
|---|---|---|
| Tier 1: treatment guidelines for curable patients | ||
| Nasopharynx | ||
| T1N0 | RT alone (2.12 Gy/fx to 69.96 Gy or 2 Gy/fx to 70 Gy) | Radiation doses and volumes per NRG‐HN001 |
| All other M0 patients | CRT (2.12 Gy/fx to 69.96 Gy or 2 Gy/fx to 70 Gy) | |
| Nasal cavity and paranasal sinuses | Surgery ± adjuvant RT (2 Gy/fx to 60‐66 Gy) ± concurrent chemotherapy | Surgery remains the standard of care when possible. |
| T1‐T4 | If surgery is not possible or for organ preservation: | If surgery is not possible or is refused by the patient, organ preservation is possible. |
| Definitive CRT: 2 Gy/fx to 70 Gy with concurrent chemotherapy | Definitive RT with proton therapy has shown excellent outcomes with 2‐y LC of 83%. 35 | |
| Consider proton therapy if feasible. | ||
| Oral cavity | Surgery ± adjuvant RT (2 Gy/fx to 60‐66 Gy) ± concurrent chemotherapy | Surgery remains the standard of care when possible. |
| T1‐T4 | If surgery will be delayed or not possible or for organ preservation: | Brachytherapy has been used as part of definitive RT for oral cavity cancers but is also limited under current restrictions on surgical interventions. 36 |
| Definitive RT (2 Gy/fx to 70 Gy) | In the setting of operating room closures, experts agree that radical RT for early oral tongue cancer and radical CRT for locally advanced oral tongue cancer are appropriate. 32 | |
| Consider proton therapy if feasible. | There is limited randomized evidence to support induction chemotherapy, which can delay surgery. 37 , 38 However, because of uncertainty about the safe reinstitution of surgery, potential detriments to the patient's immune system, and the risks of extra exposures, we caution against induction chemotherapy. | |
| Concurrent chemotherapy if T3, T4, or N+ | Definitive CRT with IMRT has been shown to achieve 2‐y LRC of 64%. 39 | |
| Highly recommend for early‐stage disease if surgery is not possible. | Because of superior dosimetry, proton therapy could be considered to deliver high doses with less toxicity. | |
| Oropharynx and unknown primary | Given equivalent outcomes with surgery and radiation, RT is favored because of public health mandates and pandemic precautions. | |
| p16‐positive | ||
| T1N0‐T2N0 | Definitive RT (2.12 Gy/fx to 69.96 Gy or 2 Gy/fx to 70 Gy) | |
| Any T3, T4, or N+ | Definitive CRT (2 Gy/fx to 70 Gy) + concurrent platinum‐based chemotherapy (prefer high‐dose cisplatin) | Because of the failure of deintensification, definitive CRT remains the standard of care for node‐positive, p16+ OPC off trial. 40 |
| p16‐negative | There is no role for modest hypofractionation in patients receiving chemotherapy because of the high likelihood of a cure and increased risks of toxicity with higher doses per fraction. 41 | |
| T1N0‐T2N0 | Definitive RT (2.12 Gy/fx to 69.96 Gy preferred or 2 Gy/fx to 70 Gy) | |
| Any T3, T4, or N+ | Definitive CRT (2 Gy/fx to 70 Gy) + concurrent platinum‐based chemotherapy | We do not recommend twice daily hyperfractionation schedules because they increase the number of visits to a clinic and thus increase exposures. |
| Larynx | Given equivalent outcomes with surgery and radiation, RT is favored because of public health mandates and pandemic precautions. | |
| T1N0 glottic larynx | Definitive RT (2.25 Gy/fx to 63 Gy) | |
| T2N0 glottic larynx | Definitive RT (2.25 Gy/fx to 65.25 Gy) | There is no role for modest hypofractionation in patients receiving chemotherapy because of the high likelihood of a cure and increased risks of toxicity with higher doses per fraction. |
| T1‐T2N0 supraglottic or subglottic larynx | Definitive RT (2 Gy/fx to 70 Gy; consider 2.12 Gy/fx to 69.96Gy) | We do not recommend twice daily hyperfractionation schedules because they increase the number of visits to a clinic and thus increase exposures. |
| T3, T4, or N+ glottic larynx; all other larynx | Definitive CRT (2 Gy/fx to 70 Gy) + concurrent platinum‐based chemotherapy | |
| Hypopharynx | ||
| T1N0‐T2N0 | Definitive RT (2.12 Gy/fx to 69.96 Gy preferred or 2 Gy/fx to 70 Gy) | Given equivalent outcomes with surgery and radiation, RT is favored because of public health mandates and pandemic precautions. |
| Any T3, T4, or N+ | Definitive CRT (2 Gy/fx to 70 Gy) + concurrent platinum‐based chemotherapy | There is no role for modest hypofractionation in patients receiving chemotherapy because of the high likelihood of a cure and increased risks of toxicity with higher doses per fraction. 41 |
| We do not recommend twice daily hyperfractionation schedules because they increase the number of visits to a clinic and thus increase exposures. | ||
| Tier 2: treatment guidelines where LRC is important | ||
| Recurrent HNC in need of reirradiation | The Multi‐Institutional Reirradiation Collaborative performed RPA to identify favorable patients for definitive reirradiation and found that hyperfractionation does not improve outcomes and may increase toxicity. 42 , 43 Absence of organ dysfunction and doses > 50 Gy are important determinants of LRC. 44 | |
| Postoperative patients | Conventionally fractionated RT (2 Gy/fx to 60‐66 Gy) | |
| No surgery: >2 y from RT or good KPS | Conventionally fractionated RT (2 Gy/fx to 70 Gy) | |
| No surgery and rapid recurrence from first course | Quad Shot (3.7 Gy/fx twice daily × 2 consecutive days = 1 cycle; may repeat cycle every 3‐4 wk for up to 4 total cycles) | |
| Metastatic HNC in need of local therapy | The RTOG Quad Shot regimen is a well‐validated treatment that achieves palliative responses in two‐thirds of patients with a grade 3 toxicity rate of only approximately 10%, even in the reirradiation setting. 45 Quad Shot can be administered with concurrent systemic therapy, is effective in multiple histologies, and is effective across all H&N subsites. | |
| Prior RT | Quad Shot (3.7 Gy/fx twice daily × 2 consecutive days = 1 cycle; may repeat cycle every 3‐4 wk for up to 4 total cycles) | |
| No prior RT | Quad Shot (3.7 Gy/fx twice daily × 2 consecutive days = 1 cycle; may repeat cycle every 3‐4 wk for up to 4 total cycles) | We favor the RTOG Quad Shot over the HYPO trial regimen (6 Gy/fx at 2/wk to 30 Gy with optional 6‐Gy boost for small disease [≤3 cm] in suitable patients) because of its potent efficacy, minimal toxicity, and universal applicability to palliative, metastatic, and reirradiation settings. 46 , 47 Furthermore, Quad Shot allows higher BED and repeat cycles versus hypofractionation. There is less daily exposure in comparison with hypofractionation. Quad Shot has been reported to be less toxic than 30 Gy/10 fx and 20 Gy/5 fx. 48 Lastly, Quad Shot is ideal during the crisis because it decreases exposures for both patients and staff and has a built‐in break between cycles. |
| Other primary cancer metastatic to H&N | Quad Shot (3.7 Gy/fx twice daily × 2 consecutive days = 1 cycle; may repeat cycle every 3‐4 wk for up to 4 total cycles) | Consider the histology, patient's performance status, and systemic therapies in selecting an appropriate treatment regimen. |
| Other palliative regimens: 30 Gy/10 fx, 20 Gy/5 fx, 8 Gy/1 fx | ||
| Tier 3: severe restrictions or limitations in radiation oncology operations | ||
| Larynx | ||
| T1N0 glottic larynx | Definitive RT (3.12‐3.28 Gy/fx to 50‐52.5 Gy; 16 fractions) | The Christie and Royal Marsden Hospital reported 93% 5‐y LC with 3 wk of RT for T1 glottic larynx cancer. 49 |
| T1‐T2N0 glottic | Definitive RT (2.55 Gy/fx to 51 Gy; 20 fractions) | Princess Margaret reported 81.7% 5‐y LC. 50 |
| Larynx | Definitive RT (2.75 Gy/fx to 55 Gy; 20 fractions) | St. James's Institute of Oncology reported 85.6% 5‐y LC. 51 |
| Oropharynx | ||
| T1‐T2N0‐N1 oropharynx | Definitive IMRT (2.2 Gy/fx to 66 Gy; 30 fractions) | In RTOG 0022, modestly accelerated hypofractionated IMRT without chemotherapy achieved 91% 2‐y LRC with reduced xerostomia in comparison with prior RTOG studies. 52 |
| p16+ T1N1‐T2N2b or T3N0‐T3N2b with ≤10‐pack‐y smoking history | Definitive CRT (2 Gy/fx to 60 Gy; 30 fractions) + concurrent platinum‐based chemotherapy | The de‐escalated CRT arm from HN002 will serve as an experimental arm of HN005. 53 |
| Locally advanced HNC | ||
| T1N0‐T4N3 SqCC of oral cavity, oropharynx, hypopharynx, or larynx | Definitive CRT (2.75 Gy/fx to 55 Gy; 20 fractions) + concurrent carboplatin | Hypofractionation accelerated CRT has been used in the United Kingdom with 79% 2‐y LC, 74% 2‐y OS, and only 9% of patients having grade 3 mucositis ≥4 wk from the onset of symptoms. 54 |
| T1‐T4N2‐N3 SqCC of oral cavity, oropharynx, hypopharynx, larynx, or unknown primary | Definitive CRT (2.75 Gy/fx to 55 Gy; 20 fractions) + concurrent cisplatin (high dose or weekly) or cetuximab | In a randomized trial of definitive chemoradiation in patients with advanced nodal disease, a minority of patients were treated with this hypofractionated schedule. 54 |
| T3‐T4N0 or any N+ SqCC of oropharynx, hypopharynx, or larynx | Definitive RT (2.55 Gy/fx to 51 Gy; 20 fractions) | A randomized trial from Princess Margaret Hospital used this regimen of hypofractionated RT alone as the standard of care. 55 |
| Compensation for Radiation Treatment Gaps | ||
|---|---|---|
| Treatment Type | Compensation | Rationale and Guiding Principles |
| RT alone | Add 1 fraction for every 1 wk of treatment gap | Treatment duration is well known to affect LC in patients treated with definitive RT. Under the assumption of 80% 2‐y LC, a 5‐d increase in duration was associated with a 3.5% reduction in LC. 56 Although there is evidence that treatment duration affects outcomes, there is no high‐level evidence that additional radiation compensates for treatment breaks. If clinical status and dosimetry permit, consider adding extra treatments as possible. |
| CRT | If the total treatment duration will be >8 wk: | There are no strong data to suggest that treatment breaks influence outcomes for patients receiving concurrent chemotherapy. |
| Reimage the patient first if the break is >1 month. | There are suggestions that a 1‐wk gap is associated with 14% to 20% reductions in LC. 57 Twice daily fractionation is easily implementable compensation because it does not require replanning and can add a dose without extending the total treatment duration. | |
|
Look at the histology and site to determine the need for additional fractions of radiation:
|
In RTOG 1016, cisplatin patients with total treatment durations of up to 58 days completed the planned course without additional fractions and with no change in total dose or dose fractionation. 58 | |
Abbreviations: BED, biologically effective dose; CRT, chemoradiotherapy; CT, computed tomography; fx, fraction(s); H&N, head and neck; HNC, head and neck cancer; IMRT, intensity‐modulated radiation therapy; KPS, Karnofsky performance status; LC, local control; LRC, locoregional control; OPC, oropharyngeal cancer; OS, overall survival; PET, positron emission tomography; RPA, recursive partitioning analysis; RT, radiation therapy; RTOG, Radiation Therapy Oncology Group; SqCC, squamous cell carcinoma.
a
Seventh edition of the American Joint Committee on Cancer staging system.