Prognostic factors of successful on-purpose tumor biopsies in metastatic cancer patients included in the SHIVA prospective clinical trial

Abstract

PURPOSETo identify patient/tumor characteristics associated with success of biopsy in patients who received multiple lines of chemotherapy.METHODSPatients with refractory cancer from our center, who were included in a prospective randomized phase II trial comparing targeted therapies based on molecular profile of tumors versus conventional chemotherapy, were retrospectively included in this IRB-approved study. All patients had a biopsy of a tumor lesion performed during surgery, or using CT/palpation/endoscopic guidance. A biopsy was considered successful if the neoplastic cellularity was greater than 30%. Primary lesion, size and location of biopsied lesion, on-going chemotherapy and the differential attenuation between non-enhanced and venous phase (HU) for CT-guided biopsied lesions were recorded.RESULTS228 patients (age=59±15yo; M/F=1.9) were included. One hundred and sixty biopsies (72%) of the 221 biopsies performed were successful. Prognostic factors of biopsy success were: no ongoing chemotherapy, surgical or palpation-guided biopsy, lymph nodes/soft tissue location(P <0.01). Among the 221 performed biopsies, 122 (55%) were performed using CT guidance and 82 (67%) were successful. In this subgroup, biopsied lesions located in lymph nodes/soft tissue were associated with a higher success rate while lung location was associated with failure (P <0.01). The mean differential attenuation was significantly higher in lesions with a successful biopsy (P <0.001).CONCLUSIONSuccess of biopsy was less frequent with CT guidance than with surgical or palpation-guided biopsy and was higher in soft tissues and lymph nodes than that in visceral metastasis. Ongoing chemotherapy decreased tumor cell content and consequently the success of the biopsy samples for molecular profiling.

Characteristics of percutaneous core biopsies adequate for next generation genomic sequencing

“…In contrast, lesions not exposed to prior systemic therapy or systemic therapy closer to time of biopsy might be less likely to have developed as much fibrosis. This finding contrasts with prior work showing that ongoing chemotherapy at the time of biopsy reduces yield [ 30 ] or has no effect on biopsy yield [ 28 ]. The difference might be attributable to the different tumor types included in those studies compared to ours.…”

“…Unlike prior studies that showed no associated between lesion size and adequacy of biopsy [ 21 , 28 , 30 ], in our study lesions <3 cm in maximal diameter had higher odds (OR 2.72) of adequacy for NGS than larger lesions on multivariate analysis. This result was unexpected because of the ease with which larger lesions are biopsied.…”

“…The type of cancer being biopsied affected the yield for NGS, a finding partially supported by a recent study that showed histological subtype influenced adequacy of biopsy [ 30 ] but other recent studies have shown no association [ 24 , 28 ]. On multivariate analysis, melanoma lesions had higher odds of adequacy for NGS than breast cancer lesions (OR 9.5).…”

“…Precision medicine holds the promise of improved outcomes by targeting patient specific molecular aberrations. Percutaneous core biopsy is a central method for acquiring material for molecular diagnosis; however, there are logistical challenges to using these specimens as evidenced by the wide spectrum of genetic sequencing adequacy of biopsy samples ranging from 39% to 95% in trials using sequencing for treatment selection with the higher yields generally found with surgical specimens, fresh frozen rather than formalin fixed specimens, or testing for fewer genes [ 21 – 30 ]. Though our reported 69.9% adequacy for NGS in a cohort of patients with histologically diagnostic biopsies is well within the reported range, the reasons for lower adequacy for NGS compared to histological diagnosis requires evaluation [ 14 ].…”

Only one step from tailored oncological therapies

“…Eligible patients are randomized to molecularly targeted therapies or to treatment at the physician's choice. Treatment cross over is possible at the time of disease progression [12,13].…”