Table 2.

Different types of guidance that can be provided by the using an upfront expanded assay that includes both secondary alterations to assess via the FDA/NCCN guidelines as well as alterations not included in the guidelines.

Case studies of clinical management change based on alterations found from expanded testing
Class of guidance	Alteration	Clinical Outcome
Extended Targets	MET exon 14 deletion	78 yr old female, never-smoker: Complete response of widely metastatic disease, including brain metastasis on crizotinib. Initially started on routine chemotherapy-2 cycles of carboplatin and pemetrexed with gamma-knife to brain lesion, but was progressing on first assessment. Started on crizotinib and had a complete response, including brain lesions on first assessment. No evidence of disease after 2 months of crizotinib. Stopped crizotinib after transaminitis, but still no evidence of disease 6 months later (Figure 4).
Potential Immunotherapy guidance	B2M p.L15Ffs*41	69 year old male: Presented with widely metastatic disease. Negative for all guideline mutations except tumor had a KRAS activating mutation, indicating resistance to TKIs. Immunotherapy was discussed, but tumor had a B2M loss-of-function, which is associated with poor immunotherapy response. Referred to hospice.
General treatment strategy: (Change in diagnosis)	TMPRSS-ERG fusion	81 yr old male with 18 year remote history of treated prostate cancer controlled with androgen deprivation therapy. New onset shortness of breath and other symptoms brought him in and he was diagnosed with widely metastastic lung adenocarcinoma and was started on traditional chemotherapy. Found to have TMPRSS-ERG fusion that is almost exclusively found in prostate cancer. Progressed on chemotherapy and then reassessed for primary prostate and lost to follow-up.