PRINCIPLES OF RADIATION THERAPY:
DEFINITIVE:
RT Alone (for T1,N0 or patients who are not eligible to receive chemotherapy)
-PTV
–High risk: Primary tumor and involved lymph nodes [this includes possible local subclinical infiltration at the primary site and at the high-risk level lymph node(s)]
—• 70–70.2 Gy (1.8–2.0 Gy/fraction); daily Monday–Friday in 7–8 weeks *,**
—• 69.96 Gy (2.12 Gy/fraction) daily Monday–Friday in 6–7 weeks
–Low to intermediate risk: Sites of suspected subclinical spread
—• 44–50 Gy (2.0 Gy/fraction) to 54–63 Gy (1.6–1.8 Gy/fraction)****
–For T1,N0,M0 disease, neck targets for elective RT to the neck include levels 7A/B, II, III, and VA.
CONCURRENT SYSTEMIC THERAPY/RT:
(preferred for patients eligible for chemotherapy)
-PTV
–High risk: Typically 70–70.2 Gy (1.8–2.0 Gy/fraction); daily Monday–Friday in 7–8 weeks*
–Low to intermediate risk: 44–50 Gy (2.0 Gy/fraction) to 54–63 Gy (1.6–1.8 Gy/fraction)***
IMRT is recommended for cancers of the nasopharynx to minimize dose to critical structures. Proton therapy can be considered when normal tissue constraints cannot be met by photon-based therapy, or when photon-based therapy causes compromise of standard radiation dosing to tumor or postoperative volumes.
Footnotes
* Care should be taken to avoid critical neural structures; therefore, 1.8 Gy/fraction can be considered.
** For doses >70 Gy, some clinicians feel that the fractionation should be slightly modified (e.g., <2.0 Gy/fraction for at least some of the treatment) to minimize toxicity. An additional 2–3 doses can be added depending on clinical circumstances.
*** Suggest 44–50 Gy in sequentially planned IMRT or 54–63 Gy with IMRT dose painting technique (dependent on dose per fraction).
SYSTEMIC THERAPY FOR NASOPHARYNGEAL CANCERS*:
• The choice of systemic therapy should be individualized based on patient characteristics (eg, PS, goals of therapy).
• Use NGS profiling and other appropriate biomarker testing to test for all PD-L1 CPS and TMB prior to treatment. (category 2B)
Induction**/Sequential Systemic Therapy
Preferred Regimens
• Gemcitabine/cisplatin (category 1 for EBV-associated disease, category 2A for non-EBV-associated disease)
• Docetaxel/cisplatin/5-FU (dose-adjusted) (category 1 for EBV-associated disease, category 2A for non-EBV-associated disease)
Other Recommended Regimens
• Cisplatin/5-FU
• Docetaxel/cisplatin (category 2B)
• Following induction, agents used with concurrent systemic therapy/RT typically include weekly cisplatin or carboplatin.
Useful in Certain Circumstances
• For M1 oligometastatic disease (PS 0–1), maintenance capecitabine without concurrent RT following induction chemotherapy is an option.
Systemic Therapy/RT Followed by Adjuvant Chemotherapy
Preferred Regimens
• Cisplatin + RT followed by cisplatin/5-FU
Other Recommended Regimens
• Cisplatin + RT followed by carboplatin/5-FU
• Cisplatin + RT without adjuvant chemotherapy***
Useful in Certain Circumstances
• If cisplatin is ineligible or intolerant, carboplatin may be used as an alternative:
o Carboplatin + RT followed by carboplatin/5-FU
• Cisplatin + RT followed by capecitabine ± induction chemotherapy**** (for EBV-associated disease, for T4, N1–3 or any T, N2–3)
Reirradiation + Concurrent Systemic Therapy
• Platinum-based regimens (eg, cisplatin, or carboplatin only if cisplatin is ineligible/intolerant)
Recurrent, Unresectable, Oligometastatic, or Metastatic Disease (with no surgery or RT option)
Preferred Regimens
First-Line*****
• Cisplatin/gemcitabine + toripalimab-tpzi (category 1)
Subsequent-Line
• Toripalimab-tpzi (if disease progression on or after platinum-containing therapy)
Other Recommended Regimens
First-Line*****
-Combination Therapy
• Cisplatin/gemcitabine (category 1)
• Cisplatin/gemcitabine + other PD-1 inhibitor (eg, pembrolizumab or nivolumab)
• Cisplatin/5-FU
• Cisplatin or carboplatin/docetaxel or paclitaxel
• Carboplatin/cetuximab
• Gemcitabine/carboplatin
• Carboplatin/gemcitabine + pembrolizumab (if non-keratinizing disease) (category 2B)
• Cisplatin/gemcitabine + penpulimab-kcqx (if non-keratinizing disease) (category 2B)
• Cisplatin/gemcitabine + tislelizumab-jsgr (category 2B)
-Single Agents
• Cisplatin
• Carboplatin
• Paclitaxel
• Docetaxel
• 5-FU
• Methotrexate
• Gemcitabine
• Capecitabine
Subsequent-Line
-Immunotherapy
• Nivolumab****** (if previously treated, recurrent or metastatic non-keratinizing disease) (category 2B)
• Pembrolizumab (if previously treated, PD-L1-positive, recurrent or metastatic disease) (category 2B)
• Penpulimab-kcqx (if non-keratinizing disease with progression on or after platinum-based chemotherapy and at least one other prior line of therapy) (category 2B)
• Tislelizumab-jsgr (category 2B)
Useful in Certain Circumstances
Subsequent-Line
• Pembrolizumab (for tumor mutational burden-high [TMB-H] tumors ≥10 mut/Mb)
Footnotes
* The recommendations are based on clinical trial data for those with EBV-associated nasopharynx cancer.
** The categories of evidence and consensus for induction therapy vary depending on site (see disease-specific site in the Head and Neck Table of Contents).
*** Use of cisplatin + RT without adjuvant chemotherapy is a category 2B recommendation for stage T3,N1–3,M0 or T4,N0–3,M0 or T0 (EBV+), N2–3,M0 nasopharyngeal cancer.
**** In a randomized phase 3 trial, 77% of patients who received metronomic capecitabine received induction chemotherapy prior to cisplatin/RT.
***** If not previously used, these regimens may be considered in subsequent-line therapy as other recommended regimens.
****** Nivolumab and hyaluronidase-nvhy subcutaneous injection may be substituted for IV nivolumab. Nivolumab and hyaluronidase-nvhy has different dosing and administration than IV nivolumab.