American Head & Neck Society

Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.

Published on by Aviram Mizrachi

AHNS Basic Science/Translational Newsletter Vol 2

Phase 2 Trial of Neoadjuvant Chemotherapy and Transoral Endoscopic Surgery With Risk-Adapted Adjuvant Therapy for Squamous Cell Carcinoma of the Head and Neck

Weiss JM, Grilley-Olson JE, Deal AM, Zevallos JP, Chera BS, Paul J, Knowles MF, Usenko D, Weissler MC, Patel S, Hayes DN, Hackman T.

From Clinical Trial. Cancer. July 2018; 124(14):2986-2992.

Article Review by Aviram Mizrachi, MD

Background / Hypothesis
In this phase II clinical trial the authors attempt to stratify patients with head and neck squamous cell carcinoma (HNSCC) undergoing trans oral surgery and select them for adjuvant treatment according to the response to neoadjuvant chemotherapy. The main endpoint of this study was response to neoadjuvant chemotherapy that may lead to de-intensification of adjuvant radiation treatment. Other endpoints were feasibility and safety of this protocol. The induction protocol success was set at >75% response rate. Furthermore, the study looked at the percentage of patients, who “avoided” adjuvant radiation, which they were eligible for by having stage III/IV disease at enrolment.

Design
The study included patients with newly diagnosed resectable HNSCC of the oral cavity, oropharynx (HPV+ and HPV-), larynx and hypopharynx. Patients with T1N0 and T2N0 disease were excluded. The neoadjuvant regimen consisted of weekly carboplatin and paclitaxel and daily lapatinib for 6 weeks. Imaging was obtained 2-5 weeks following the completion of neoadjuvant treatment for evaluation of clinical response. Subsequently the patients underwent trans oral surgical resection of the primary tumor and neck dissection. Patients with pN0 and pN1 disease were observed. Adjuvant treatment included concomitant radiation plus cisplatin and was given to patients with adverse features.

(Figure 1).

Summary of Results
A total 40 patients were accrued for the trial and 37 completed the full protocol.
The majority of patients had oropharyngeal cancer (75%) however only 17 had RTOG low-risk HPV+ cancer. The clinical response rate for all patients was 93% with 40% achieving complete clinical response. Pathological complete response was observed in 36% of patients with no correlation between clinical and pathological responses. Overall, 30 patients (77%) successfully avoided adjuvant radiation. At a median follow up of 2.4 years none of the patients had recurred or died.

Toxicity in general was mild with diarrhea being the most common adverse event (lapatinib) and neutropenia being the most severe, accounting for grade 3 and 4 toxicity in 38% of patients. Finally, the functional outcomes reported in the study were excellent in terms of speech and swallowing.

Strengths

  • The study demonstrated high clinical and pathological response rates to neoadjuvant
    chemotherapy in patients with advanced stage resectable HNSCC.
  • The majority of patients successfully avoided adjuvant radiation therapy.
  • None of the patients experienced recurrence or death during follow-up.
  • Toxicity profile for this neoadjuvant regimen was relatively modest and well tolerable.
  • Functional outcomes were good, probably due to the fact that most patients did not

 Weaknesses

  • Small number of participants.
  • Heterogeneity of tumor sub-sites and especially the inclusion of HPV+ oropharyngeal
    cancer.
  • The majority of patients were RTOG low and medium risk.
  • The choice of lapatinib as a neoadjuvant agent while there is not enough evidence to
    support its use in HNSCC.

Key Points

  • Neoadjuvant regimens are emerging and may play an important role in the stratification
    and management of patients with HNSCC.
  • Specifically, the neoadjuvant regimen of Carboplatin and Paclitaxel achieved excellent
    clinical and pathological response rates.
  • The ability to de-intensify treatment by avoiding adjuvant radiation is made possible
    with neoadjuvant therapy followed by surgery, which provides valuable clinical and
    pathological insights.
  • De-intensification of adjuvant treatment may result in better functional outcomes and
    improved quality of life without compromising survival.
  • Ongoing clinical trials combining immunotherapy in neoadjuvant regimens are showing
    promising preliminary results.

From the Basic Science/Translational Service
Jeffrey C. Liu MD Vice Chair
Richard Wong MD Chair

Aviram Mizrachi

Aviram Mizrachi

Dr. Aviram Mizrachi is a surgeon-scientist at the Department of Otolaryngology – Head and Neck Surgery of Rabin Medical Center in Israel. He has an active research laboratory focusing on tumor and radiation biology in head and neck cancer as well as targeted drug delivery. Furthermore, he investigates both radiation and chemotherapy mechanisms of action and their effect on tumor and normal tissue including the utility of novel radio-sensitizing and radio-protective agents. In addition, Dr. Mizrachi conducts clinical research on outcomes in head and neck, skin and thyroid cancers.

Published on by AHNS Office

AHNS Journal Club – April Issue

Volume 30 – April, 2020

The AHNS Journal Club reviews the leading head and neck cancer-related journals, sharing with AHNS members some of the most relevant and important manuscripts, and providing summaries and critiques of the work.

The Journal Club members are: Samer Al-Khudari, MD; Daniel Brickman, MD; Nathan Hales, MD FACS; Jason Kass, MD PhD; Luiz Kowalski, MD PhD; Vikas Mehta, MD MPH FACS; Alirio Mijares Brinez, MD; Alvaro Sanabria, PhD; Mark Varvares, MD; Vivian Wu, MD MPH.

CLICK THE ARTICLES BELOW TO ACCESS THE APRIL ISSUE

Postoperative opioid-prescribing practices in otolaryngology: A multiphasic study.
Dang S, Duffy A, Li JC, Gandee Z, Rana T, Gunville B, Zhan T, Curry J, Luginbuhl A, Cottrill E, Cognetti D.
from Laryngyscope, March 2020

Selective neck dissection in the treatment of head and neck squamous cell carcinoma patients with a clinically positive neck
López F, Fernández-Vañes L, García-Cabo P, Grilli G, Álvarez-Marcos C, Llorente JL, Rodrigo JP.
from The Journal of Clinical Oncology, January 2020

Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus–Associated Oropharynx Squamous Cell Carcinoma
Ma DJ, Price KA, Moore EJ, Patel SH, Hinni ML, Garcia JJ, Graner DE, Foster NR, Ginos B, Neben-Wittich M, Garces YI, Chintakuntlawar AV, Price DL, Olsen KD, Van Abel KM, Kasperbauer JL, Janus JR, Waddle M, Miller R, Shiraishi S, Foote RL.
from The Journal of Clinical Oncology, August 2019.

Lymph node yield, depth of invasion, and survival in node-negative oral cavity cancer
Zenga J, Divi V, Stadler M, Massey B, Campbell B, Shukla M, Awan M, Schultz C, Shreenivas A, Wong S, Jackson R, Pipkorn P.
from Oral Oncology, November 2019

Published on by Ehab Hanna

COVID vs Cancer: Impact on Head and Neck Oncology

The Head & Neck journal has a new special issue, COVID-19 versus Cancer: Impact on Head and Neck Oncology, to help head and neck oncologists all over the world in dealing with the pertinent issues surrounding the challenges they face during this pandemic. The issue is available for free full content download, globally using this link https://authorea.com/inst/20973

Dr. Ehab Hanna, the Editor in Chief, introduced the issue in his Editorial, How Fragile We Are, highlighting the impact on health care systems, cancer care, and education. The editorial also discussed the issues of routine testing prior to cancer care, and our collective response to this pandemic. You can read the Editorial by using this link https://authorea.com/users/5588/articles/441050-how-fragile-we-are?commit=23e42f11eac47d7863d8b36ff84b737ecf247c68

 

Ehab Hanna

Ehab Hanna

Ehab Y. Hanna, MD FACS is Professor and Vice Chair of the Department of Head and Neck Surgery at The University of Texas MD Anderson Cancer Center in Houston, Texas. He is currently the President of the American Head & Neck Society.
Ehab Hanna

Latest posts by Ehab Hanna (see all)

Published on by Joseph Goodman

AHNS Basic Science/Translational Newsletter Vol 1

Pathologic response to neoadjuvant chemotherapy in HPV-associated oropharynx cancer

Sadeghi N, Khalife S, Mascarella MA, Ramanakumar AV, Richardson K, Joshi AS, Bouganim N, Taheri R, Fuson A, Siegel R.

From Head and Neck, March 2020;42(3):417-425.

Article Review by Joe Goodman, MD

Background / Hypothesis
According to the authors, a paradigm shift is underway leading to de-escalation trials for HPV-associated oropharynx cancer (OPC). Because of the excellent prognosis for most HPV OPC, efforts have been made to improve quality-of-life after treatment and reduce treatment-related morbidity. While most de-escalation trials have looked at reducing radiation dose or eliminating chemotherapy, this trial uses neoadjuvant chemo therapy plus transoral surgery (NAC+S) with the goal of avoiding post-op radiation based on surgical pathology.

Design
This is a prospective cohort of patients with p16+ OPC (stage III/IV AJCC 7th) treated with chemotherapy consisting of 3 cycles of cisplatin/docetaxel every 3 weeks followed by transoral surgery and neck dissection. N3 disease was excluded. All 54 patients demonstrated at least partial response to the chemotherapy regimen based on preoperative post-treatment imaging. Goal was to correlate reduction in tumor volume with likelihood of complete pathologic response pCR. Surgical pathology was assessed for presence of primary tumor and neck metastases to determine yTNM restaging and assess need for postoperative XRT. Partial response was defined as any residual tumor. MRI response of tumor was also correlated with pathological response, but not RECIST criteria because often pathological response was underpredicted by imaging response.

Summary of Results
Surgical pathology showed overall pCR of 44%, with 72% pCR at the primary and 57% pCR in the neck.

96% had negative margins. There were 3 mortalities. Preop imaging volume reduction of 90% or greater had predictive value for pCR (sensitivity 0.82 and specificity 0.73). More patients at all stages showed pCR than PR on surgical pathology although this was not specifically analyzed.

Strengths

  • Building on several other small series to show efficacy of neoadjuvant chemotherapy regimen based on surgical pathology, justifying de-escalation strategies
  • Since transoral robotic surgery involves en bloc resections of radical tonsil or base of tongue, as well as neck dissection, less likelihood of missing a small discontiguous positive margin vs endoscopic partial resection

 Weaknesses

  • Mortality of 5.6% seems high, not well explained if they declined recommended post-op treatment
  • Survival outcomes not analyzed but this data is forthcoming
  • No real attempt at understanding cellular mechanisms for this phenomenon
  • Not powered to analyze based on smoking status as possible contributor to biological response in p16+ OPC
  • While toxicity seems acceptable, long-term studies will need to be done

Key Points

  • There seems significant biological response of p16+ OPC to this particular neoadjuvant chemotherapy regimen of cisplatin and taxotere. Other regimens have been studied, for instance the Weiss article from UNC, as well as bioselection papers from UM for larynx cancer.
  • Even the original VA study showed 30% CR.
  • While the current treatment paradigm states that chemotherapy is never sufficient for primary treatment of squamous cell carcinoma, in many cases in this series there was no evidence of tumor at the primary site or in the neck as assessed on surgical pathology. This speaks to the possible for bioselection strategies using NAC+S for de-escalation in p16+ OPC.
  • Also supports an increased role for transoral surgery with good functional outcomes after neoadjuvant chemotherapy, avoiding “triple-therapy”—unless dictated by adverse features on surgical pathology – Supports role of post-chemotherapy pre-operative imaging to predict likelihood of pathologic complete response to further refine the treatment algorithm
  • Long term, multi-institutional studies of disease free survival and toxicity will need to be done

From the Basic Science/Translational Section
Jeffrey C. Liu MD Vice Chair
Richard Wong Md Chair

Joseph Goodman

Joseph Goodman

Dr. Goodman is currently Assistant Professor of Otolaryngology and Associate Residency Program Director at The George Washington University in Washington, DC. He serves as a member of the Basic and Translational Science Service of the AHNS and is a working group member of the Salivary Gland Section. His research interests include HPV-related oropharyngeal cancer and reconstructive surgery of the Head and Neck.
Joseph Goodman

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AHNS International Conference Postponed to 2021

In light of the recent concerns about COVID-19 and the growing number of travel bans placed on both international and domestic colleagues, the AHNS Leadership has elected to postpone the AHNS 10th International Conference until July 22nd-25th 2021. This decision was made to preserve the health and safety of our attendees and patients.

Abstract Submissions

We will release all submitted oral and poster submissions and re-open abstract submissions in the Summer of 2020 if you would like to re-submit your abstract with our without updates or new research for consideration at the 2021 International Meeting.

We realize you’ve worked hard on your research and don’t want to delay disseminating the information for another year; therefore we encourage you to submit your manuscripts to JAMA Otolaryngology – Head & Neck Surgery.

Faculty Assignments

If you have been invited as faculty for the July 2020 Conference, look for your invitation over the next several months!  We anticipate that the vast majority of program will be the same.  The Program Committee will review the revised 2021 scientific program and re-assign and schedule faculty soon.

Hotel Reservations

If you have made your hotel reservations, please contact the Hyatt Regency Chicago directly to cancel.  You may contact them at (877) 803-7534 or use the Passkey link provided below.

https://www.hyatt.com/en-US/group-booking/CHIRC/G-GAHN

Registration Fees

For those who Have paid your registration to attend the July 2020 Conference, your fees will be refunded to the payment option you provided when registering.

We apologize for any inconvenience to our members and attendees.

Thank you for your understanding and continued support.

Robert Ferris, MD, PhD – AHNS 2021 Conference Chair
Eben Rosenthal, MD – AHNS 2021 Program Chair
Cherie-Ann Nathan, MD, FACS – AHNS President