Induction Chemotherapy for HNSCC
Induction Chemotherapy for HNSCC
Induction Chemotherapy for Head and Neck SCC
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
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
- MTX
- 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)
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. NCT04454489 - +pembro)
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