Acute and Long-Term Effects of Chemoradiation Therapy in Head and Neck Cancer

Evaluating Adjuvant Therapy With Chemoradiation vs Radiation Alone for Patients With HPV-Negative N2a Head and Neck Cancer

“…11,[24][25][26] Because adding chemotherapy to adjuvant RT is associated with significant increases in acute-and late-treatment toxicity, it is important to precisely define which groups of patients benefit. [3][4][5] By showing that the addition of adjuvant chemotherapy in patients with pN2a HPV-negative HNSCC who had ENE and underwent margin-negative resection was not associated with improved OS, our study provides hypothesis-generating data that can be used to inform future investigation to help develop therapeutic protocols that maximize oncologic outcomes while minimizing treatment-related morbidity. Our precisely defined cohort was chosen to identify a lowerrisk ENE-positive HNSCC subgroup.…”

“…Since the publication of these trials, further precision and risk stratification within ENE-positive disease has occurred based on the number of ENE-positive LNs, extent of ENE (ie, macroscopic vs microscopic), and HPV status . Because adding chemotherapy to adjuvant RT is associated with significant increases in acute- and late-treatment toxicity, it is important to precisely define which groups of patients benefit . By showing that the addition of adjuvant chemotherapy in patients with pN2a HPV-negative HNSCC who had ENE and underwent margin-negative resection was not associated with improved OS, our study provides hypothesis-generating data that can be used to inform future investigation to help develop therapeutic protocols that maximize oncologic outcomes while minimizing treatment-related morbidity.…”

“…Standard of care per National Comprehensive Cancer Network guidelines for pathologic extranodal extension (ENE)–positive HNSCC, based on 2 landmark randomized clinical trials (RCTs), is adjuvant CRT . Although adding chemotherapy concurrent with adjuvant RT improved disease-free survival (DFS) in Radiation Therapy Oncology Group (RTOG) 9501 and overall survival (OS) in European Organization for Research and Treatment of Cancer Trial (EORTC) 22931, it also significantly increased short- and long-term morbidity and contributed to decreased functional outcomes …”

“…2 Although adding chemotherapy concurrent with adjuvant RT improved disease-free survival (DFS) in Radiation Therapy Oncology Group (RTOG) 9501 and overall survival (OS) in European Organization for Research and Treatment of Cancer Trial (EORTC) 22931, it also significantly increased short-and long-term morbidity and contributed to decreased functional outcomes. [3][4][5] The American Joint Committee on Cancer Staging Manual, 8th Edition (AJCC8), introduced pathologic ENE into the staging criteria for HPV-negative HNSCC. 6,7 This led to the creation of 2 new nodal classifications for patients with HPVnegative HNSCC: pN2a for those with a single positive lymph node (LN) smaller than 3 cm with pathologic ENE, and pN3b for those with pathologic ENE in a single LN larger than 3 cm or in multiple LNs.…”

Microscopic Extranodal Extension in HPV‐Negative Head and Neck Cancer and the Role of Adjuvant Chemoradiation

“…33 Nevertheless, these collective trials established adjuvant CRT as standard of care for patients with ENE per National Comprehensive Cancer Network guidelines and the basis of high-risk surgically resected HNSCC for subsequent cooperative group trials. 8,34,35 However, because of the significant morbidity associated with cytotoxic chemotherapy concurrent with RT that was also evident in the long-term follow-up of RTOG 9501, 36 there has been an intense effort to define precisely the subset of high-risk patients who benefit from CRT. 34,35,[37][38][39] Because ENE was assessed in a dichotomous fashion (present/absent) in these landmark trials, whether the oncologic benefit of adjuvant CRT applies equally regardless of the extent of ENE (microscopic or macroscopic) is not known.…”