Important Studies

Question 1

Benefit of Chemo

Answer 1

MAC-NPC: Petit et al, ASCO, 2020. 8221 “Nasopharynx
All subtypes” “Meta-analysis of 28 trials.

Induction with taxane gave best OS when evaluating individual types of chemo

When combining all types of chemo, adjuvant chemo had better OS than induction”

Question 2

Chemo Sequencing

Answer 2

Zhang et al, JAMA Netw Open, 2019: 8036 Nasopharynx. “Meta-analysis of 28 randomized trials to evaluate benefit of neoadjuvant, concurrent, and adjuvant chemo

Induction chemo and concurrent chemo should be recommended in nasopharynx cancer. Adjuvant chemo should be avoided.

Question 3

CCRT+adjuvant chemo vs. RT alone

Answer 3

INT 0099: Al-Sarraf et al, JCO, 1998. 193 Stage III-IV→70 Gy vs. 70 Gy + concurrent cisplatin x3 & adj cisplatin 5FU x3. “3-yr OS 78% vs. 47%. 5-yr OS 67% vs 37%. Concurrent and adjuvant chemo added to RT results in OS benefit in nasopharynx.

Question 4

Chemo sequencing with conventional vs. 6fx weekly

Answer 4

Lee et al, Cancer, 2020. 803 nasopharynx Stage III-IVB, nonkeratinizing
"6 arms: 
1) adj PF, conventional RT
2) ind PF, conventional RT
3) ind PX, conventional RT
4) adj PF, 6 fx weekly RT
5) ind PF, 6 fx weekly RT
6) ind PX, 6 fx weekly RT"

“No difference with RT regimens
Overall, no difference in induction/adj

On exploratory analysis, some difference with induction/adj with conventional RT only:
5-yr PFS 78% vs. 62%
5-yr OS 84% vs. 72%
better PFS with PX over PF induction
5-yr PFS 78% vs. 62%"

Induction chemotherapy with PX may improve PFS and OS compared to adjuvant chemotherapy with conventionally fractionated RT.

Question 5

Concurrent chemo

Answer 5

Taichung Veterans Hospital, Taiwan: Lin et al, JCO, 2003. 284 Stage III-IV M0 WHO grade I-III”→70-74 Gy
vs. 70-74 Gy with concurrent cisplatin 5FU. “5-yr OS 54% vs 72%, 5-yr PFS 53% vs 72%

Sun Yat-sen University, Guangzhou, China: Chen et al, JNCI, 2011. 1992 T1-2N1 or T2N0 with parapharyngeal involvement, WHO grade II-III"→68-70 Gy alone vs. 68-70 Gy with weekly cisplatin. 
Chemo RT improved OS, PFS, DMFS, LRC:
5-yr OS 86% vs 95%
5-yr LRC 91% vs 93%
5-yr PFS 78% vs 88%
5-yr DMFS 84% vs 95%"

Question 6

Adjuvant chemo

Answer 6

Sun Yat-sen University, Guangzhou, China: Chen et al, Lancet Oncol, 2012. 251 “Stage III/IV (not T3 or T4)
nonkeratinizing. RT to ≥66 Gy in 2.0-2.27 Gy / fx with concurrent weekly cisplatin → adjuvant cisplatin 5FU x3
vs. no adjuvant.
2-yr FFS 86% vs 84%, p=0.13
2-yr OS 94% vs 92%, p=0.32
2-yr DMS 88% vs 86%, p=0.12
2-yr LRFFS 98% vs 95%, p=0.10
There is no benefit to adjuvant chemotherapy.

Question 7

Induction chemo

Answer 7

Sun Yat-sen University, Guangzhou, China: Sun et al, Lancet Oncol, 2016. 241 Stage III-IVB nonkeratinizing “→Induction TPF then RT with cisplatin vs. chemoRT alone. Addition of induction TPF to chemoRT improved FFS. Longer term follow-up is needed.

Sun Yat-sen University, Guangzhou, China: Zhang et al, NEJM, 2019. 480 Stage IIIB-IVB nonkeratinizing. “gem/cis induction vs. no induction prior to chemoRT.
“3-yr RFS 85% vs. 77%
3-yr OS 95% vs. 90%
acute grade 3-4 toxicity 76% vs. 56%
late grade 3-4 toxicity 9% vs. 11%”
Induction chemo added to chemoRT improves RFS and OS compared to no induction chemo.

National Cancer Centre Singapore, Singapore: Tan et al, IJROBP, 2015. 172 Nasopharynx WHO II-III”→RT with concurrent weekly cisplatin vs. induction gem/carbo/paclitaxel x2 with chemoRT.
No difference in 3-yr OS, 92% GCP vs 94%.
No difference in DFS or DMFS
There is no benefit to induction chemotherapy in nasopharynx cancer.

Question 8

Treatment of primary in Stage IV

Answer 8

Sun Yat-sen University: You et al, JAMA Oncol, 2020. 126 Metastatic nasopharynx cancer with CR or PR after PF x3 (only 1.5% were keratininzing). “PF x3, then if CR or PR→PF x6 then 70 Gy IMRT to primary vs. PF x6
2-yr OS 76% C+RT vs. 55% chemo
2-yr DM 54% vs 68%
2-yr PFS 35% vs. 4%
Locoregional treatment in metastatic nasopharynx cancer improves OS and reduces DM.

Question 9

EBV testing for adjuvant chemo

Answer 9

NRG-HN001 (ongoing). Stage II-IVB with detectable EBV DNA.

RT with concurrent cisplatin, then test EBV DNA. Then
if detectable EBV, then consolidation 5-FU/cisplatin x3 vs gem/paclitaxel x4 if undetectable EBV, then consolidation 5-FU/cisplatin x3 vs obs”

Question 10

IMRT

Answer 10

RTOG 0225: Lee et al, JCO, 2009. 68 Nasopharynx Stage I-IVB. IMRT to 70 Gy/59.4 Gy in 33 fx. For ≥T2b or N+: concurrent cisplatin and adjuvant cis/5FU.
2 yr LC 92%, 2 yr OS 80%, 2-yr regional PFS 91%, 2-yr DMF 86%
acute grade 4 mucositis 4%, late grade 3 dysphagia 5%, xerostomia 3%, long term PEG 4%

Outcomes with this IMRT SIB regimen are improved over Intergroup 0099.