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Induction Chemotherapy for Head and Neck SCC

beau hilton, 2024-07-18

current

Case presentation

61M, previously healthy. Heavy smoker, quit a couple of months ago.

5 weeks of progressive facial pain.

Seen by local doctors, given antibiotics for a presumed sinus infection.

Purulent drainage.

Dentures stopped fitting.

Face started to go numb.

Admitted, biopsied.

Nasopharyngeal SCC, nonkeratinizing, discharged home.

No notes.

Induction Chemotherapy for Head and Neck SCC

beau hilton, 2024-07-18

Case presentation

61M, previously healthy. Heavy smoker, quit a couple of months ago.

5 weeks of progressive facial pain.

Seen by local doctors, given antibiotics for a presumed sinus infection.

Purulent drainage.

Dentures stopped fitting.

Face started to go numb.

Admitted, biopsied.

Nasopharyngeal SCC, nonkeratinizing, discharged home.

Case presentation

Exam

Swollen left eye

Numb left cheek and lips

Labs

mild anemia, mild leukocytosis, BMP and LFTs fine, really nothing interesting

Imaging

Similar case on Radiopaedia:

https://radiopaedia.org/cases/59258/studies/66600?lang=us

Questions

What is induction? (What is the difference between induction and neoadjuvant therapy?)
When is induction a good idea?
When is it a bad idea?
Why are the surgeons always asking us to induce?
What regimens are available/have been studied?
How do I select a regimen for a given patient and situation?

induction chemotherapy (ICT) through the ages

1960s

1970s

MTX vs cisplatin (response rate 14-41%)
cisplatin+bleomycin
cisplatin+bleomycin+[MTX vs vinca]
- cisplatin+bleomycin+vincristine response rate 80%, CR 29%
cisplatin+5-FU (PF)
- response rate 88%, CR 19%
PF with 120h of 5-FU
- response rate 93%, Cr 38%
PF with 120h of 5-FU and higher dose of cisplatin
- no benefit, more tox

ICT through the ages

1980s

5x RCT w MTX - 4/5 -ve, 1/5 +ve only for stage II oral cavity disease (and used intra-arterial MTX)
many other RCTs, no benefit (outside of limited stage oral cavity disease)

1990s

Concurrent Cisplatin-based chemoRadioTherapy (CCRT)

Lacas et al 2021, Radiotherapy and Oncology

ICT through the ages

2000s

PF vs TPF
European study (TAX323) had RT afterward, American Study (TAX324) had CCRT afterward.

ICT through the ages

2000s

ICT + CCRT vs CCRT alone
OS doesn’t increase, toxicity does
nuanced (locoregional vs distant recurrence)
later meta-analyses suggest perhaps TPF+CCRT has benefit over CCRT alone (fitter patients?)

ICT through the ages

2010s

Rise of the mods:

modified TPF (dose reduced)
weekly carbo-taxol followed by CCRT
TPEx (cisplatin, docetaxel, cetuximab)

Our patient:

docetaxel 75, cisplatin 75, q3wk x3 and reimage

ICT today

NPC
- gem+cis ICT f/b CCRT: +OS benefit if EBV+ (NEJM 2019, JCO 2022)
larynx preservation
- CCRT not clearly better than ICT in pts who qualify for total laryngectomy but not partial - SALTORL trial is comparing ICT and CCRT head-to-head
treatment intensification
- TPF+CCRT in the fittest patients?
converting borderline resectable to resectable
- ~30% conversion rate
oligometastatic disease
- shrink/eliminate distant sites, spot weld prn, then CCRT/surgery?
neurologic and airway compromise (i.e. true urgencies, nonoperable)
- dental procedures wrt timing of RT, may need to start ICT to bridge until dental procedures are done plus ~2wks (h/t Ronak Mistry)

ICT for NPC

Induction radiotherapy?

"Quad-shot" RT: 14-15 Gy over 4 fractions

2x/day (6h separation) x 2 days
palliative
if response, can continue monthly (usually cap around Gy in the low 40s)
studies looking at quad-shot+something are ongoing (e.g. http://clinicaltrials.gov/study/NCT04454489 - +pembro)

Resources

Bibliography

Ferrari, Daris, Maria Grazia Ghi, Ciro Franzese, Carla Codecà, Max Gau, and Jerome Fayette. “The Slippery Role of Induction Chemotherapy in Head and Neck Cancer: Myth and Reality.” Frontiers in Oncology 10 (January 23, 2020): 7. https://doi.org/10.3389/fonc.2020.00007.

Jacobs, John R., Thomas F. Pajak, Jeannie Kinzie, Muhyi Al-Sarraf, Lawrence Davis, Gerald A. Hanks, Irving Weigensberg, and Steven Leibel. “Induction Chemotherapy in Advanced Head and Neck Cancer: A Radiation Therapy Oncology Group Study.” Archives of Otolaryngology–Head & Neck Surgery 113, no. 2 (February 1, 1987): 193–97. https://doi.org/10.1001/archotol.1987.01860020085018.

Okano, Susumu, Akihiro Homma, Naomi Kiyota, Makoto Tahara, Nobuhiro Hanai, Takahiro Asakage, Kazuto Matsuura, et al. “Induction Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck.” Japanese Journal of Clinical Oncology 51, no. 2 (February 1, 2021): 173–79. https://doi.org/10.1093/jjco/hyaa220.

Vermorken, Jan B. “Where and When to Use Induction Chemotherapy in Head and Neck Squamous Cell Cancer.” In Critical Issues in Head and Neck Oncology, edited by Jan B. Vermorken, Volker Budach, C. René Leemans, Jean-Pascal Machiels, Piero Nicolai, and Brian O’Sullivan, 155–79. Cham: Springer International Publishing, 2021. https://doi.org/10.1007/978-3-030-63234-2_11.

Lacas, B., Carmel, A., Landais, C., Wong, S. J., Licitra, L., Tobias, J. S., Burtness, B., Ghi, M. G., Cohen, E. E. W., Grau, C., Wolf, G., Hitt, R., Corvò, R., Budach, V., Kumar, S., Laskar, S. G., Mazeron, J.-J., Zhong, L.-P., Dobrowsky, W., … Zackrisson, B. (2021). Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group. Radiotherapy and Oncology, 156, 281–293. https://doi.org/10.1016/j.radonc.2021.01.013