case_images: PMC11103604_01
case_images: Cases 1 and 2 (PACC/classical compound EGFR mutation). (A) I Timeline of Case 1. II, III. May 2017. Tumor staging pT2a pN0 M0, St. IIA UICC 8. IV. August 2017. A single symptomatic metastasis and infiltration of the major psoas was detected. V. January 2020. Adrenal metastases detected. VI. August 2020. Disease progression was observed in the area of the former adrenal gland. (B) Timeline of Case 2. *Single symptomatic metastasis and infiltration of the major psoas.  488.12 mg carboplatin AUC 80%; 796 mg pemetrexed 80%. ABCP, atezolizumab plus bevacizumab plus carboplatin plus paclitaxel; AE, adverse event; DOR, duration of response; G, grade; NGS, next generation sequencing; NSCLC, non-small cell lung cancer; PACC, P-loop and alphaC-helix compressing; PD, progressive disease; Q4W, every 4 weeks; RT, radiotherapy; UICC, Union for International Cancer Control.
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case_images: PMC11103604_02_fonc-14-1347742-g001.jpg
case_images: f1
case_images: NSCLC (stage IVB; programmed death-ligand 1 [PD-L1]: 1%; pulmonary and bone metastases) ( Figure 1B ). NGS (QIAseq Custom Lung Panel, Qiagen) identified a novel compound mutation comprising substitution mutations on exon 18 (G719A, PACC) and exon 21 (L861R, classical-like).
case_images: PMC11103604_02
case_images: Cases 1 and 2 (PACC/classical compound EGFR mutation). (A) I Timeline of Case 1. II, III. May 2017. Tumor staging pT2a pN0 M0, St. IIA UICC 8. IV. August 2017. A single symptomatic metastasis and infiltration of the major psoas was detected. V. January 2020. Adrenal metastases detected. VI. August 2020. Disease progression was observed in the area of the former adrenal gland. (B) Timeline of Case 2. *Single symptomatic metastasis and infiltration of the major psoas.  488.12 mg carboplatin AUC 80%; 796 mg pemetrexed 80%. ABCP, atezolizumab plus bevacizumab plus carboplatin plus paclitaxel; AE, adverse event; DOR, duration of response; G, grade; NGS, next generation sequencing; NSCLC, non-small cell lung cancer; PACC, P-loop and alphaC-helix compressing; PD, progressive disease; Q4W, every 4 weeks; RT, radiotherapy; UICC, Union for International Cancer Control.
case_images: fonc-14-1347742-g001.jpg
case_images: PMC11103604_02_fonc-14-1347742-g001.jpg
case_images: f1
case_images: NSCLC (stage IVB; programmed death-ligand 1 [PD-L1]: 1%; pulmonary and bone metastases) ( Figure 1B ). NGS (QIAseq Custom Lung Panel, Qiagen) identified a novel compound mutation comprising substitution mutations on exon 18 (G719A, PACC) and exon 21 (L861R, classical-like).
case_images: PMC11103604_03
case_images: Cases 3 and 4. (PACC exon 18 deletion insertion mutation) (A) Timeline of Case 3. Afatinib was discontinued in January 2022 at the patient's request. In May 2023, progression of the lung metastases was observed following a CT scan. Afatinib was resumed and PR was observed in July 2023. As of September 2023, the patient remains symptom free. (B) Timeline of Case 4. *Nov 2017: palliative RT (thoracic spine, lumbar, Os pubis left [5 Gy/Fraction]. WBRT: Nov-Dec 2017. Zoledronic acid: Dec 2017-Jun 2018. First-line treatment with erlotinib: Dec 2017-Jun 2018. Second-line treatment with afatinib: Jun-Sep 2018. AE, adverse event; G, grade; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; PACC, P-loop and alphaC-helix compressing; PD, progressive disease; PR, partial response; Q3W, every 3 weeks; RT, radiotherapy; TTF-1, thyroid transcription factor-1; WBRT, whole brain radiotherapy.
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case_images: PMC11103604_04_fonc-14-1347742-g002.jpg
case_images: f2
case_images: A 64-year-old female was diagnosed with NSCLC (stage IVB) in November 2017 during workup of a painful pathologic fracture in the 8th thoracic vertebra ( Figure 2B ).
case_images: PMC11103604_04
case_images: Cases 3 and 4. (PACC exon 18 deletion insertion mutation) (A) Timeline of Case 3. Afatinib was discontinued in January 2022 at the patient's request. In May 2023, progression of the lung metastases was observed following a CT scan. Afatinib was resumed and PR was observed in July 2023. As of September 2023, the patient remains symptom free. (B) Timeline of Case 4. *Nov 2017: palliative RT (thoracic spine, lumbar, Os pubis left [5 Gy/Fraction]. WBRT: Nov-Dec 2017. Zoledronic acid: Dec 2017-Jun 2018. First-line treatment with erlotinib: Dec 2017-Jun 2018. Second-line treatment with afatinib: Jun-Sep 2018. AE, adverse event; G, grade; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; PACC, P-loop and alphaC-helix compressing; PD, progressive disease; PR, partial response; Q3W, every 3 weeks; RT, radiotherapy; TTF-1, thyroid transcription factor-1; WBRT, whole brain radiotherapy.
case_images: fonc-14-1347742-g002.jpg
case_images: PMC11103604_04_fonc-14-1347742-g002.jpg
case_images: f2
case_images: A 64-year-old female was diagnosed with NSCLC (stage IVB) in November 2017 during workup of a painful pathologic fracture in the 8th thoracic vertebra ( Figure 2B ).
case_images: PMC11103604_05
case_images: Cases 5 and 6 (novel substitution mutations) (A) Timeline of Case 5. (B) Timeline of Case 6. *whole brain radiotherapy. CDKN2A, cyclin-dependent kinase inhibitor 2A; EGFR, epidermal growth factor receptor; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; PD, progressive disease; PR, partial response; QD, each day; RT, radiotherapy; SD, stable disease; TP53, tumor protein 53.
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case_images: f3
case_images: In September 2018, an asymptomatic 65-year-old male with a history of arterial hypertension, latent diabetes mellitus, and degenerative spinal syndrome, was diagnosed with NSCLC (stage IIIA/IV) following magnetic resonance imaging examination of the cervical spine ( Figure 3B ); suspicious enlargement of the left adrenal gland was also observed.
case_images: PMC11103604_06
case_images: Cases 5 and 6 (novel substitution mutations) (A) Timeline of Case 5. (B) Timeline of Case 6. *whole brain radiotherapy. CDKN2A, cyclin-dependent kinase inhibitor 2A; EGFR, epidermal growth factor receptor; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; PD, progressive disease; PR, partial response; QD, each day; RT, radiotherapy; SD, stable disease; TP53, tumor protein 53.
case_images: fonc-14-1347742-g003.jpg
case_images: PMC11103604_06_fonc-14-1347742-g003.jpg
case_images: f3
case_images: In September 2018, an asymptomatic 65-year-old male with a history of arterial hypertension, latent diabetes mellitus, and degenerative spinal syndrome, was diagnosed with NSCLC (stage IIIA/IV) following magnetic resonance imaging examination of the cervical spine ( Figure 3B ); suspicious enlargement of the left adrenal gland was also observed.
case_images: PMC11103604_07
case_images: Case 7 (novel EGFR::CCDC6 fusion) I. Timeline of Case 1. II. April 2023. III. May 2023, New bilateral pulmonary metastases detected. IV. July 2023. Restaging: no detectable pulmonary metastases, regression of primary lesion. Ex, Exon; UICC, Union for International Cancer Control.
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case_images: PMC11103604_07_fonc-14-1347742-g004.jpg
case_images: f4
case_images: First-line treatment (carboplatin/pemetrexed/pembrolizumab +- vibostolimab/denusomab) as part of the KeyVibe-007 trial (EUDRA-CT: 2021-004564-94) began in January 2023 ( Figure 4 ).