TABLE A1.
Case Number, Diagnosis, Age at Diagnosis, Pediatric Oncologists' Perceptions of NTRK-Fused Tumor Results, Impact on Clinical Management, Time to Start Larotrectinib, and Current Medication Usage by Patients (data censored on September 1, 2023)
| No. | Pathologic Diagnosis | Age at Diagnosis, Months | How NGS Results and Access to NTRK Inhibitors Helped Pediatric Oncologists to Better Assist Their Patients, According to Their Own Clinical Perception? | Time to Start NTRK Inhibitor Therapy (Too Early/Proper/Late) | Is the Patient Still on Therapy With a NTRK Inhibitor? |
|---|---|---|---|---|---|
| 1 | WHO grade IV analogous malignant glioneuronal tumor | 53.9 | Treatment with conventional chemotherapy was not effective | Proper | No |
| 2 | Infantile fibrosarcoma | 13.3 | The result helped in the therapeutic planning and targeted therapy with good clinical results | Late | No |
| 3 | Pediatric high-grade glioma | 10.9 | The result allowed us to request target drug (larotrectinib); radiation therapy was avoided for this child, with good clinical outcome | Proper | No |
| 4 | Grade II diffuse astrocytoma | 8.5 | The result allowed us to prescribe larotrectinib, with a very good clinical outcome | Late | No |
| 5 | Infantile fibrosarcoma | 14.3 | We were allowed to prescribe NTRK inhibitor and avoid other cytotoxic treatments | Proper | No |
| 6 | Peripheral nerve sheath sarcoma | 34.4 | The patient had already used chemotherapy and radiotherapy, without remission of the disease. Patient already had sequelae related to surgical procedures—no additional treatment options | Late | Yes |
| 7 | Diffuse glioneuronal tumor with similar oligodendroglial features and nuclear clusters | 159.5 | Targeted therapy was able to be offered, after conventional treatments have shown little success | Too early | No |
| 8 | Infantile fibrosarcoma | 3.3 | Patient with poor response to conventional chemotherapy | Proper | No |
| 9 | Infantile fibrosarcoma | 7.4 | Oral treatment, with lesser toxicity, outpatient, making it possible not to use traditional cytotoxic chemotherapy, dispensing the use of long-term catheters | Late | No |
| 10 | Neuroblastoma | 8.8 | Primary posterior mediastinal neuroblastoma with spinal canal invasion. Surgery difficult to perform (high morbidity). Change of treatment (conventional intravenous chemotherapy) to specific oral medication | Proper | No |
| 11 | Low-grade soft tissue sarcoma, NOE | 39.7 | Patient did not respond to conventional chemotherapy and showed a lot of toxicity; treatment with larotrectinib offered excellent quality of life and partial clinical response on imaging | Proper | Yes |
| 12 | Infantile fibrosarcoma | 8.6 | The tumor did not shrink with any conventional chemotherapy as per the 2005 EpSSG NRTS Protocol for localized non-rabdo sarcomas. In the second cycle of more intensive chemotherapy, the patient had an anaphylactic reaction | Proper | No |
| 13 | Infantile fibrosarcoma | 0.1 | Microscopic margins compromised by the tumor (difficult tumor location at abdomen); decision about offering neoadjuvant therapy (in infants) with available target therapy (as opposed to offering chemotherapy) was preferred | Proper | Yes |
| 14 | Infantile fibrosarcoma | 1.5 | Large tumor, inoperable because of its location on the face, poorly responsive to chemotherapy | Late | No |
| 15 | Mesenchymal spindle cell sarcoma/malignant peripheral nerve sheath tumor | 40.1 | Patient initially received intensive chemotherapy, without response and with many adverse effects | Late | Yes |
| 16 | Infantile fibrosarcoma | 3.2 | Helped us to manage a tumor weighting 477 g in child weighing 4.8 kg; surgical margins compromised; therapy used as adjunctive therapy | Proper | No |
| 17 | Low-grade glioma | 90.8 | Exhaustion of therapeutic resources; the result allowed us to offer novel therapy to this case | Late | No |
NOTE. Observations: These are qualitative and descriptive data about the personal impression of the physician responsible for the patient's treatment regarding the time window between the prescription of the NTRK inhibitor medication and its actual availability for patient use (early, proper, or late). Data from column 4 were free translations of reports from the attending physicians regarding their own perception of how NGS results and access to the NTRK inhibitor may have affected the health care of their patients.
Abbreviations: NGS, next-generation sequencing; NOE, not otherwise specified; NTRK, neurotrophic tropomyosin receptor kinase.