Long-Term Survival after High-Dose Chemotherapy Followed by Peripheral Stem Cell Rescue for High-Risk, Locally Advanced/Inflammatory, and Metastatic Breast Cancer

Patients with high-risk locally advanced/inflammatory and oligometastatic (≤3 sites) breast cancer frequently relapse or experience early progression. High-dose chemotherapy combined with peripheral stem cell rescue may prolong progression-free survival/relapse-free survival (PFS/RFS) and overall survival (OS). In this study, patients initiated high-dose chemotherapy with STAMP-V (carboplatin, thiotepa, and cyclophosphamide), ACT (doxorubicin, paclitaxel, and cyclophosphamide), or tandem melphalan and STAMP-V. Eighty-six patients were diagnosed with locally advanced/inflammatory (17 inflammatory) breast cancer, and 12 were diagnosed with oligometastatic breast cancer. Median follow-up was 84 months (range, 6-136 months) for patients with locally advanced cancer and 40 months (range, 24-62 months) for those with metastatic cancer. In the patients with locally advanced cancer, 5-year RFS and OS were 53% (95% CI, 41%-63%) and 71% (95% CI, 60%-80%), respectively, hormone receptors were positive in 74%, and HER2 overexpression was seen in 23%. In multivariate analysis, hormone receptor–positive disease and lower stage were associated with better 5-year RFS (60% for ER [estrogen receptor]/PR [progesterone receptor]-positive versus 30% for ER/PR-negative; P < .01) and OS (83% for ER/PR-positive versus 38% for ER/PR-negative; P < .001). In the patients with metastatic cancer, 3-year PFS and OS were 49% (95% CI, 19%-73%) and 73% (95% CI, 38%-91%), respectively. The favorable long-term RFS/PFS and OS for high-dose chemotherapy with peripheral stem cell rescue in this selected patient population reflect the relative safety of the procedure and warrant validation in defined subgroups through prospective, randomized, multi-institutional trials

Idiopathic Popliteal Artery Pseudoaneurysm: Emergency Diagnosis And Treatment [pseudoaneurisma Idiopático Da Artéria Poplítea: Abordagem Diagnóstico-terapêutica Na Urgência]

Pseudoaneurysms or false aneurysms of the popliteal artery are uncommon arterial disorders. These disorders most commonly result from trauma and iatrogenic lesions following orthopedic procedures. The authors report a rare case of popliteal artery pseudoaneurysm in which etiology was unknown. The authors also demonstrate that Doppler ultrasonography may be sufficient for planning vascular surgical procedures and that the open surgical approach is the treatment of choice for cases in which the symptomatic lesion causes local compression.133244248Tedesco, M.M., Dalman, R.L., Arterial aneurysms (2010) Rutherford's Vascular Surgery, pp. 559-615. , In: Cronenwett JL, Johnston KW, editors, 7th ed. Philadelphia: ElsevierMiyamotto, M., Moreira, R.C.R., Erzinger, F.L., França, G.J., Cunha, A.G.P., Pseudo-aneurisma idiopático da artéria poplítea (2004) J Vasc Bras, 3 (2), pp. 169-171Gillespie, D.L., Cantelmo, N.L., Traumatic popliteal artery pseudoaneurysms: Case report and review of the literature (1991) J Trauma, 31 (3), pp. 412-415. , http://dx.doi.org/10.1097/00005373-199103000-00019, PMid: 2002532Bel Haj Salah, R., Triki, W., Gherib, S.B., Ben Moussa, M., Zaouche, A., Traumatic popliteal artery pseudo aneurysm (2011) Tunis Med, 89 (8-9), pp. 721-722. , PMid: 21948669Szyber, P., Jr., Skóra, J., Rybak, W., Pupka, A., Iatrogenic pseudoaneurysm of the popliteal artery following corrective tibial osteotomy (2011) Vasa, 40 (5), pp. 414-417. , http://dx.doi.org/10.1024/0301-1526/a000140, PMid: 21948786Tsuji, Y., Kitano, I., Iida, O., Kajita, S., Sawada, K., Nanto, S., Popliteal pseudoaneurysm caused by stent fracture (2011) Ann Vasc Surg, 25 (6), pp. 840.e5-840.e8. , http://dx.doi.org/10.1016/j.avsg.2010.12.039, PMid: 21620667Kao, C.L., Chang, J.P., Pseudoaneurysm of the popliteal artery: A rare sequela of acupuncture (2002) Tex Heart Inst J, 29 (2), pp. 126-129. , PMid: 12075870Pavić, P., Vergles, D., Sarlija, M., Ajduk, M., Cupurdija, K., Pseudoaneurysm of the popliteal artery in a patient with multiple hereditary exostoses (2011) Ann Vasc Surg, 25 (2), pp. 268.e1-268.e2. , http://dx.doi.org/10.1016/j.avsg.2010.07.027, PMid: 20926234Pellenc, Q., Capdevila, C., Julia, P., Fabiani, J.N., Ruptured popliteal artery pseudoaneurysm complicating a femoral osteochondroma in a young patient (2012) J Vasc Surg, 55 (4), pp. 1164-1165. , http://dx.doi.org/10.1016/j.jvs.2011.01.060, PMid: 21459549Ge, P.S., Ishaque, B.M., Bonilla, J., de Virgilio, C., Popliteal artery pseudoaneurysm after isolated hyperextension of the knee (2010) Ann Vasc Surg, 24 (7), pp. 950.e7-950.e11. , http://dx.doi.org/10.1016/j.avsg.2010.01.014, PMid: 20471789Koksoy, C., Gyedu, A., Alacayir, I., Bengisun, U., Uncu, H., Anadol, E., Surgical treatment of peripheral aneurysms in patients with Behcet's disease (2011) Eur J Vasc Endovasc Surg, 42 (4), pp. 525-530. , http://dx.doi.org/10.1016/j.ejvs.2011.05.010, PMid: 21641238Ghassani, A., Delva, J.C., Berard, X., Deglise, S., Ducasse, E., Midy, D., Stent graft exclusion of a ruptured mycotic popliteal pseudoaneurysm complicating sternoclavicular joint infection (2012) Ann Vasc Surg, 26 (5), pp. 730.e13-730.e15. , http://dx.doi.org/10.1016/j.avsg.2011.09.015, PMid: 22664287Erler, K., Ozdemir, M.T., Oguz, E., Basbozkurt, M., Does false aneurysm behave like a sarcoma? Distal femoral arterial false aneurysm simulated a malign mesenchymal tumor. A case report and review of the literature (2004) Arch Orthop Trauma Surg, 124 (1), pp. 60-63. , http://dx.doi.org/10.1007/s00402-003-0595-8, PMid: 14576956Kim, Y.J., Baek, W.K., Kim, J.Y., Pseudoaneurysm of the popliteal artery mimicking tumorous condition (2011) J Korean Surg Soc, 80, pp. S71-S74. , http://dx.doi.org/10.4174/jkss.2011.80.Suppl1.S71, PMid: 2206609Fitzgerald, E.J., Bowsher, W.G., Ruttley, M.S., False aneurysm of the femoral artery: Computed tomographic and ultrasound appearances (1986) Clin Radiol, 37 (6), pp. 585-588. , http://dx.doi.org/10.1016/S0009-9260(86)80033-2, PMid: 3539457Callcut, R.A., Acher, C.W., Hoch, J., Tefera, G., Turnipseed, W., Mell, M.W., Impact of intraoperative arteriography on limb salvage for traumatic popliteal artery injury (2009) J Trauma, 67 (2), pp. 252-257. , http://dx.doi.org/10.1097/TA.0b013e31819ea796, PMid: 19667876, discussion 257-8Proia, R.R., Walsh, D.B., Nelson, P.R., Early results of infragenicular revascularization based solely on duplex arteriography (2001) J Vasc Surg, 33 (6), pp. 1165-1170. , http://dx.doi.org/10.1067/mva.2001.115376, PMid: 11389413Ascher, E., Hingorani, A., Markevich, N., Costa, T., Kallakuri, S., Khanimoy, Y., Lower extremity revascularization without preoperative contrast arteriography: Experience with duplex ultrasound arterial mapping in 485 cases (2002) Ann Vasc Surg, 16 (1), pp. 108-114. , http://dx.doi.org/10.1007/s10016-001-0130-8, PMid: 11904814Pulli, R., Dorigo, W., Castelli, P., A multicentric experience with open surgical repair and endovascular exclusion of popliteal artery aneurysms (2013) Eur J Vasc Endovasc Surg, 45 (4), pp. 357-363. , http://dx.doi.org/10.1016/j.ejvs.2013.01.012, PMid: 23391602Trinidad-Hernandez, M., Ricotta, J.J., II, Gloviczki, P., Results of elective and emergency endovascular repairs of popliteal artery aneurysms (2013) J Vasc Surg, 57 (5), pp. 1299-1305. , http://dx.doi.org/10.1016/j.jvs.2012.10.112, PMid: 23375609Zaraca, F., Ponzoni, A., Stringari, C., Ebner, J.A., Giovannetti, R., Ebner, H., The posterior approach in the treatment of popliteal artery aneurysm: Feasibility and analysis of outcome (2010) Ann Vasc Surg, 24 (7), pp. 863-870. , http://dx.doi.org/10.1016/j.avsg.2010.04.005, PMid: 2083198

Long-term safety and efficacy of tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study

Background Tezacaftor–ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8–24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOLVE]) or heterozygous for the Phe508del CFTR mutation and a residual function mutation (F/RF; study 661-108 [EXPAND]). Longer-term (>24 weeks) safety and efficacy of tezacaftor–ivacaftor has not been assessed in clinical studies. Here, we present results of study 661-110 (EXTEND), a 96-week open-label extension study that assessed long-term safety, tolerability, and efficacy of tezacaftor–ivacaftor in participants aged 12 years or older with cystic fibrosis who were homozygous or heterozygous for the Phe508del CFTR mutation. Methods Study 661-110 was a 96-week, phase 3, multicentre, open-label study at 170 clinical research sites in Australia, Europe, Israel, and North America. Participants were aged 12 years or older, had cystic fibrosis, were homozygous or heterozygous for Phe508del CFTR, and completed one of six parent studies of tezacaftor–ivacaftor: studies 661-103, 661-106, 661-107, 661-108, 661-109, and 661-111. Participants received oral tezacaftor 100 mg once daily and oral ivacaftor 150 mg once every 12 h for up to 96 weeks. The primary endpoint was safety and tolerability. Secondary endpoints were changes in lung function, nutritional parameters, and respiratory symptom scores; pulmonary exacerbations; and pharmacokinetic parameters. A post-hoc analysis assessed the rate of lung function decline in F/F participants who received up to 120 weeks of tezacaftor–ivacaftor in studies 661-106 (F/F) and/or 661-110 compared with a matched cohort of CFTR modulator-untreated historical F/F controls from the Cystic Fibrosis Foundation Patient Registry. Primary safety analyses were done in all participants from all six parent studies who received at least one dose of study drug during this study. This study was registered at ClinicalTrials.gov (NCT02565914). Findings Between Aug 31, 2015, to May 31, 2019, 1044 participants were enrolled in study 661-110 from the six parent studies of whom 1042 participants received at least one dose of study drug and were included in the safety set. 995 (95%) participants had at least one TEAE; 22 (2%) had TEAEs leading to discontinuation; and 351 (34%) had serious TEAEs. No deaths occurred during the treatment-emergent period; after the treatment-emergent period, two deaths occurred, which were both deemed unrelated to study drug. F/F (106/110; n=459) and F/RF (108/110; n=226) participants beginning tezacaftor–ivacaftor in study 661-110 had improvements in efficacy endpoints consistent with parent studies; improvements in lung function and nutritional parameters and reductions in pulmonary exacerbations observed in the tezacaftor–ivacaftor groups in the parent studies were generally maintained in study 661-110 for an additional 96 weeks. Pharmacokinetic parameters were also similar to those in the parent studies. The annualised rate of lung function decline was 61·5% (95% CI 35·8 to 86·1) lower in tezacaftor–ivacaftor-treated F/F participants versus untreated matched historical controls. Interpretation Tezacaftor–ivacaftor was generally safe, well tolerated, and efficacious for up to 120 weeks, and the safety profile of tezacaftor–ivacaftor in study 661-110 was consistent with cystic fibrosis manifestations and with the safety profiles of the parent studies. The rate of lung function decline was significantly reduced in F/F participants, consistent with cystic fibrosis disease modification. Our results support the clinical benefit of long-term tezacaftor–ivacaftor treatment for people aged 12 years or older with cystic fibrosis with F/F or F/RF genotypes. Funding Vertex Pharmaceuticals Incorporated