RESUMEN
Undifferentiated sarcoma of the liver is rare, especially in adults, and is an aggressive malignancy that originates from the primary mesenchymal tissues. A 53-year-old man was referred to our hospital for further evaluation of a low-grade fever. Contrast-enhanced CT revealed an 18-cm tumor in the right lobe of the liver. The tumor was characterized by low-density areas suspected of cystic components, a high-density area suspected of hemorrhage, and contrast enhancement in the thickened marginal and internal septa. MRI revealed a high-intensity tumor with a heterogeneous structure on T2-weighted images. Angiosarcoma of the liver with intratumoral hemorrhage was suspected, and right hepatectomy was performed. The pathological diagnosis was an undifferentiated sarcoma based on the presence of undifferentiated mesenchymal tumor cells with a stellate to spindle-shaped pleomorphism. Following a multidisciplinary discussion, 4 courses of the AI regimen (doxorubicin and ifosfamide)were administered as adjuvant chemotherapy, and no recurrence was confirmed at 2 years and 6 months follow-up. Our case suggests that radical resection followed by adjuvant chemotherapy may contribute to a favorable prognosis for undifferentiated sarcoma of the liver.
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Protocolos de Quimioterapia Combinada Antineoplásica , Doxorrubicina , Hepatectomía , Neoplasias Hepáticas , Sarcoma , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Sarcoma/tratamiento farmacológico , Sarcoma/cirugía , Quimioterapia Adyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Doxorrubicina/administración & dosificación , Ifosfamida/administración & dosificaciónRESUMEN
PURPOSE: Paclitaxel, ifosfamide, and cisplatin (TIP) is an established salvage regimen for germ cell tumors (GCT) on the basis of a phase II trial, but efficacy on a large patient cohort including patients with unfavorable risk features and long-term outcomes has not been reported. Herein, we report updated treatment efficacy and long-term follow-up with TIP. PATIENTS AND METHODS: Patients with GCT who received TIP after cisplatin-based chemotherapy were eligible. Favorable response (complete response or partial response with negative tumor markers), overall survival (OS) and progression-free survival (PFS) rates, relapse, and toxicity were determined. Disease was reclassified according to the International Prognostic Factor Study Group (IPFSG) score. RESULTS: Of the 104 patients, 87 had favorable risk factors and 17 had at least one unfavorable factor by Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Ten patients were treated for a second gonadal primary GCT. With a median follow-up of 8.9 years, the 5-year PFS and OS rates were 66% (95% CI, 55 to 74) and 69% (95% CI, 59 to 77), respectively. Among 87 patients with favorable-risk disease, 69 (79%) achieved a favorable response with 5-year PFS and OS rates of 67% (95% CI, 56 to 76) and 72% (95% CI, 61 to 80), respectively. Among 17 patients with MSKCC unfavorable-risk disease, 13 (76%) achieved a favorable response with 5-year PFS and OS rates of 59% (95% CI, 33 to 78) and 56% (95% CI, 28 to 76), respectively. After IPFSG reclassification, 5-year PFS and OS rates for patients with ≤intermediate-risk disease were 75% (95% CI, 50 to 89) and 73% (95% CI, 55 to 85), respectively. CONCLUSION: TIP is an effective second-line regimen for patients with GCT. Similar outcomes were observed in patients with favorable- and unfavorable-risk disease. The randomized TIGER trial (ClinicalTrials.gov identifier: NCT02375204) comparing TIP with high-dose chemotherapy will determine the optimal second-line treatment approach.
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Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Ifosfamida , Neoplasias de Células Germinales y Embrionarias , Paclitaxel , Terapia Recuperativa , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Estudios de Seguimiento , Ifosfamida/administración & dosificación , Ifosfamida/uso terapéutico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias de Células Germinales y Embrionarias/patología , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Resultado del Tratamiento , Ensayos Clínicos como AsuntoRESUMEN
RATIONALE: We report a phase II trial (OSAD93) testing CDDP with ifosfamide (IFO), without doxorubicin in neoadjuvant phase, in adult osteosarcoma with a 25 years follow-up. PATIENTS AND METHODS: This is a multicentric phase II study of neoadjuvant chemotherapy with IFO and CDDP in localized high-grade osteosarcoma of patients. Patients received 4 pre-operative courses of IFO 9 g/m2 and CDDP 100 mg/m2 on day 4 (SHOC regimen), followed by local treatment. Doxorubicin was added post-operatively (HOCA regimen) in patients with > 10 % residual tumor cells. A Good Histological Response (GHR), ie ≤ 10 % residual tumor cells in > 30 % of patients, was the primary objective. Disease-free survival (DFS), overall survival (OS) and toxicity were secondary objectives. RESULTS: From Jan 1994 to Jun 1998, 60 patients were included. Median age was 27 (range: 16-63). Primary tumor sites were limbs (76 %), trunk, head or neck (24 %). After neoadjuvant SHOC, grade 3-4 and febrile neutropenia, thrombopenia, and re-hospitalization occurred in 58 %, 17 %, 17 % and 22 % of SHOC courses and in 76 %, 28 %, 47 %, 47 % of HOCA courses, respectively. GHR was obtained in 16/60 (27.5 %) patients. With a median follow-up of 322 months, the DFS and OS were 51.8 % and 64.4 % at 5 years. At 10 years, DFS and OS were 49.9 % and 64.4 %. At 25 years, DFS and OS were 47.8 % and 55.9 %. No long-term cardiac toxicity was observed. Three patients developed a second malignancy (one fatal) after 300 months. CONCLUSION: Though the primary endpoint of OSAD93 was not met, this pre-operative doxorubicin-free regimen led to excellent long-term survival with limited toxicity in localized osteosarcoma.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Óseas , Ifosfamida , Osteosarcoma , Humanos , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/mortalidad , Osteosarcoma/patología , Adulto , Masculino , Femenino , Persona de Mediana Edad , Adulto Joven , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Ifosfamida/uso terapéutico , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/mortalidad , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Supervivencia sin Enfermedad , Estudios de SeguimientoRESUMEN
INTRODUCTION: Ewing sarcoma (ES), is a rare cancer affecting children, adolescents and adults. After VIDE (vincristine-ifosfamide-doxorobucin-etoposide) induction chemotherapy, Busulfan-Melphalan (BuMel) high-dose chemotherapy followed by autologous hematopoietic stem cells transplantation improved outcomes in unfavourable localized ES, but with more toxicities than conventional chemotherapy (VAI: Vincristine-dactinomycin-Ifosfamide). We evaluated whether the risk of acute toxicity associated with BuMel compared to VAI varied according to age in patients recruited in the R2Loc and R2Pulm randomised trials of the Euro-E.W.I.N.G.99 and Ewing-2008 trials. METHODS: We included patients with a localized high-risk disease, or pulmonary or pleural metastasis. We analysed the risk of severe toxicity according to randomised treatment group (VAI versus BuMel) and age group (<12 years, 12-17 years, 18-24 years, ≥25 years). We evaluated the heterogeneity of treatment effects by age group using interaction terms in logistic multivariable models. RESULTS: The analysis included 243 patients treated with VAI and 205 with BuMel. Overall, BuMel was associated with a higher risk of severe acute toxicity than VAI particularly haematological, gastrointestinal, liver, sinusoidal occlusive syndrome, and infections. Severe haematological toxicity and lower general condition were significantly more frequent in younger patients, whatever treatment. We did not observe any significant heterogeneity in terms of the excess risk of severe toxicities associated with BuMel compared to VAI according to age group. CONCLUSION: The excess of acute toxicity associated with BuMel compared to VAI does not vary significantly with age, suggesting the feasibility of BuMel across all age groups.
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Protocolos de Quimioterapia Combinada Antineoplásica , Busulfano , Trasplante de Células Madre Hematopoyéticas , Melfalán , Sarcoma de Ewing , Trasplante Autólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/terapia , Busulfano/administración & dosificación , Busulfano/efectos adversos , Niño , Adolescente , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Melfalán/administración & dosificación , Melfalán/efectos adversos , Melfalán/uso terapéutico , Masculino , Femenino , Factores de Edad , Adulto , Etopósido/administración & dosificación , Etopósido/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Vincristina/efectos adversos , Vincristina/administración & dosificación , Vincristina/uso terapéutico , Preescolar , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Resultado del TratamientoRESUMEN
Cyclophosphamide and ifosfamide are major alkylating agents but their therapeutics uses are limiting by the toxicity due to several toxicities. Indeed conventional chemotherapies are generally used with the maximum tolerated dose. In contrast, metronomic schedule aims to get a minimum dose for efficacy with a good safety. Depending on the dose, their mechanisms of action are different and offer a dual activity: at high dose, cyclophosphamide is mainly used in graft conditioning for its immunosuppressive properties, while at metronomic dose it is used as an immunoactive agent. Currently, at metronomic dose, cyclophosphamide is studied in clinic against various types of cancer, alone or in combination with others anticancer drugs (anti-angiogenic, immune-modulating agents, immune checkpoints blockers, vaccines, radiotherapy, others conventional anticancer agents), as a nth-line or first-line treatment. More than three quarters of clinical studies show promising results, mostly in breast, ovarian and prostate cancers. Taking advantage of the immune system, use dual antitumor action's chemotherapy is clearly a therapeutic strategy that deserves to be confirmed in order to improve the efficacy/toxicity balance of anticancer treatments, and to use CPM or analogues as a standard of care.
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Ciclofosfamida , Neoplasias , Humanos , Ciclofosfamida/farmacología , Ciclofosfamida/administración & dosificación , Neoplasias/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Alquilantes/administración & dosificación , Administración Metronómica , Ifosfamida/administración & dosificación , Relación Dosis-Respuesta a DrogaRESUMEN
BACKGROUND: Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?" and CQ #2, "Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?". METHODS: A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain. RESULTS: Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval. CONCLUSION: This review indicated that G-CSF's efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma.
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Protocolos de Quimioterapia Combinada Antineoplásica , Factor Estimulante de Colonias de Granulocitos , Sarcoma de Ewing , Humanos , Sarcoma de Ewing/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Japón , Neoplasias Óseas/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Doxorrubicina/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/administración & dosificación , Calidad de Vida , Etopósido/uso terapéutico , Etopósido/administración & dosificación , Ifosfamida/uso terapéutico , Ifosfamida/efectos adversos , Ifosfamida/administración & dosificación , Oncología Médica/métodos , Vincristina/uso terapéutico , Vincristina/efectos adversosRESUMEN
BACKGROUND: The prognosis of patients with Relapsed/Refractory Osteosarcoma (R/R OS) remains dismal without an agreement on systemic therapy. The use of High-Dose Ifosfamide (14 g/sqm) with an external pump in outpatient setting (14-IFO) in R/R OS patients is limited. This study represents the first retrospective cohort analysis focused on evaluating the activity and toxicity of 14-IFO in this setting. PATIENTS AND METHODS: The study investigated 14-IFO activity, in terms of tumour response according to RECIST 1.1 criteria, as well as survival rates and toxicity, according to CTCAE v.5. RESULTS: The trial enrolled 26 patients with R/R OS. The Overall Response Rate (ORR) and Disease Control Rate (DCR) obtained was 23% and 57.5%, respectively. Patients with relapsed OS showed a higher ORR (45%) and DCR (82%) compared to refractory patients, irrespective of the number of prior treatment lines received. The achievement of disease control with 14-IFO administration enabled 27% of patients to undergo new local treatment. Four-month Progression-Free Survival (PFS) was 54% for all patients and 82% for the relapsed OS sub-group. Median Overall Survival (OSurv) was 13.7 months, with 1-year OSurv of 51% for all patients and 71% for relapsed patients. Age over 18 years and the presence of refractory disease were identified as negative prognostic factors for this patient cohort. A total of 101 cycles were evaluated for toxic assessment, demonstrating a tolerable profile without grade 3-4 non-haematological toxicities. CONCLUSIONS: 14-IFO should be considered a viable treatment option for R/R OS, particularly due to its well tolerated toxicity profile and the potential for home-administration, which can improve patient quality of life without compromising efficacy.
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Neoplasias Óseas , Ifosfamida , Recurrencia Local de Neoplasia , Osteosarcoma , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Ifosfamida/uso terapéutico , Masculino , Femenino , Estudios Retrospectivos , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/mortalidad , Osteosarcoma/patología , Adulto , Adolescente , Adulto Joven , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Persona de Mediana Edad , Niño , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos Alquilantes/efectos adversos , Clasificación del Tumor , Resultado del TratamientoRESUMEN
BACKGROUND: Treatment options are limited, and the prognosis is poor for patients with platinum-resistant recurrent metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). This study evaluated the efficacy and safety of a paclitaxel and ifosfamide (TI) regimen in patients with R/M HNSCC whose disease had progressed following platinum-based therapy. PATIENTS AND METHODS: In this retrospective study, we included 53 patients with R/M HNSCC who underwent at least one cycle of TI-based therapy, post platinum failure, between February 2020 and August 2023. Some patients received the TI regimen in combination with immunotherapy and/or cetuximab. Key metrics assessed included the objective response rate (ORR), disease control rate, and progression-free as well as overall survival. RESULTS: The study observed an ORR of 15.8% and a disease control rate of 36.8%. The median progression-free survival for the entire cohort was 3.3 months, and the median overall survival was 9.6 months. Notably, the combination of TI with immunotherapy yielded a higher ORR of 30.8%, compared to 14.3% with TI alone. The most prevalent grade 1-2 adverse events were anemia (81%), weight loss (68%) and hypernatremia (55%). CONCLUSION: The TI-based regimen demonstrated favorable efficacy and safety profile in treating R/M HNSCC. Enhanced outcomes may be attainable when combining it with immunotherapy. This study suggests that TI-based therapy could serve as a potential salvage option for this specific patient group.
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Protocolos de Quimioterapia Combinada Antineoplásica , Resistencia a Antineoplásicos , Neoplasias de Cabeza y Cuello , Ifosfamida , Recurrencia Local de Neoplasia , Paclitaxel , Terapia Recuperativa , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Adulto , Ifosfamida/uso terapéutico , Ifosfamida/administración & dosificación , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Platino (Metal)/uso terapéutico , Metástasis de la Neoplasia , Anciano de 80 o más Años , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: There is limited evidence regarding the systemic treatment of retroperitoneal soft-tissue sarcoma, and the current Japanese guidelines fail to make definitive suggestions. Here, we report our experience with combination chemotherapy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in this population. PATIENTS AND METHODS: We retrospectively reviewed the records of eight patients (three male and five female) who received MAID for pathologically diagnosed metastatic unresectable retroperitoneal sarcoma (either leiomyosarcoma or pleomorphic sarcoma) between October 2019 and January 2022. Treatment efficacy, tolerability (need for dose reduction), and safety profiles were evaluated and summarized. RESULTS: At initiation, the median age was 56.0 years, and the body mass index was 20.0 kg/cm2 Six patients had Eastern Cooperative Oncology Group performance status scores of 0. The net clinical benefit was a partial response in three (37.5%) patients, stable disease in four (50.0%), and progressive disease in one (12.5%). During the median 90.8 weeks of follow-up, disease in five patients progressed, resulting in a median progression-free survival of 48.4 weeks, and five deaths occurred, resulting in an overall survival of 95.1 weeks. Commonly observed adverse events were neutropenia (eight patients), anemia (eight patients), and decreased platelet count (seven patients), which led to dose reduction (60-80%) in six patients. CONCLUSION: MAID combination therapy may be an acceptable option for advanced retroperitoneal sarcoma; however, its benefits must be carefully assessed owing to its not insignificant toxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica , Dacarbazina , Doxorrubicina , Ifosfamida , Mesna , Neoplasias Retroperitoneales , Sarcoma , Humanos , Masculino , Femenino , Persona de Mediana Edad , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Retroperitoneales/tratamiento farmacológico , Neoplasias Retroperitoneales/patología , Sarcoma/tratamiento farmacológico , Sarcoma/patología , Mesna/administración & dosificación , Mesna/uso terapéutico , Anciano , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Dacarbazina/uso terapéutico , Estudios Retrospectivos , AdultoRESUMEN
BACKGROUND: In retrospective analyses, the Pediatric Oncology Group [POG) and the Federation National des Centres de Lutte Contre le Cancer (FNCLCC) histologic grade predict outcome in pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), but prospective data on grading, clinical features, and outcomes of low-grade NRSTS are limited. METHODS: We analyzed patients less than 30 years of age enrolled on Children's Oncology Group (COG) study ARST0332 (NCT00346164) with POG grade 1 or 2 NRSTS. Low-risk patients were treated with surgery alone. Intermediate-/high-risk patients received ifosfamide/doxorubicin and radiotherapy, with definitive resection either before or after 12 weeks of chemoradiotherapy. RESULTS: Estimated 5-year event-free and overall survival were 90% and 100% low risk (n = 80), 55% and 78% intermediate risk (n = 15), and 25% and 25% high risk (n = 4). In low-risk patients, only local recurrence was seen in 10%; none with margins greater than 1 mm recurred locally. Sixteen of 17 intermediate-/high-risk patients who completed neoadjuvant chemoradiotherapy underwent gross total tumor resection, 80% with negative margins. Intermediate-/high-risk group events included one local and seven metastatic recurrences. Had the FNCLCC grading system been used to direct treatment, 29% of low-risk (surgery alone) patients would have received radiotherapy ± chemotherapy. CONCLUSIONS: Most low-risk patients with completely resected POG low-grade NRSTS are successfully treated with surgery alone, and surgical margins greater than 1 mm may be sufficient to prevent local recurrence. Patients with intermediate- and high-risk low-grade NRSTS have outcomes similar to patients with high-grade histology, and require more effective therapies. Use of the current FNCLCC grading system may result in overtreatment of low-risk NRSTS curable with surgery alone.
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Sarcoma , Humanos , Femenino , Masculino , Niño , Adolescente , Sarcoma/terapia , Sarcoma/patología , Sarcoma/mortalidad , Preescolar , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto Joven , Lactante , Adulto , Tasa de Supervivencia , Clasificación del Tumor , Estudios Retrospectivos , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Estudios de Seguimiento , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Ifosfamida/administración & dosificación , Pronóstico , Neoplasias de los Tejidos Blandos/terapia , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/mortalidad , Estudios Prospectivos , Terapia CombinadaRESUMEN
INTRODUCTION: The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy. METHODS: We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1-3 plus etoposide 750 mg/m2 on days 1-3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment-related complications and survival outcomes were recorded. RESULTS: The median age of the patients was 31 (range 18-62). The median follow-up was 31.1 months (95% CI, 28.9-33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1-43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival (OS) rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline. CONCLUSION: One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%.
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Protocolos de Quimioterapia Combinada Antineoplásica , Trasplante de Células Madre Hematopoyéticas , Recurrencia Local de Neoplasia , Neoplasias de Células Germinales y Embrionarias , Terapia Recuperativa , Trasplante Autólogo , Humanos , Terapia Recuperativa/métodos , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/mortalidad , Adulto , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adolescente , Trasplante de Células Madre Hematopoyéticas/métodos , Femenino , Etopósido/uso terapéutico , Etopósido/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/administración & dosificación , Carboplatino/uso terapéutico , Carboplatino/administración & dosificación , Ifosfamida/administración & dosificación , Ifosfamida/uso terapéutico , Resultado del Tratamiento , Terapia Combinada , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéuticoRESUMEN
BACKGROUND: Embryonal sarcoma of the liver (ESL) is a rare mesenchymal tumor most common in childhood; the optimal treatment approach is uncertain. The clinical features and outcomes of patients with ESL enrolled in a Children's Oncology Group (COG) clinical trial that evaluated a risk-based strategy for treating soft tissue sarcomas in patients aged <30 years were evaluated. METHODS: This subset analysis included patients with ESL enrolled in COG study ARST0332. Central review of records, pathology, and imaging confirmed the diagnosis, presenting features, and surgery extent and complications. All patients received dose-intensive ifosfamide/doxorubicin chemotherapy, with cycle timing dependent on surgery and radiotherapy. Tumor resection occurred before study entry or after four cycles of chemotherapy; radiotherapy for residual tumor was optional. RESULTS: Thirty-nine eligible/evaluable patients with ESL were analyzed. All tumors were >10 cm in diameter; four were metastatic. Tumor resection was performed upfront in 23 and delayed in 16. Positive surgical margins (n = 6) and intraoperative tumor rupture (n = 6) occurred only in upfront resections. Eight patients received radiotherapy. Estimated 5-year event-free and overall survival were 79% (95% confidence interval [CI], 65%-93%) and 95% (95% CI, 87%-100%), respectively. Positive margins increased the local recurrence risk. One of 13 patients with documented hemorrhagic ascites and/or tumor rupture developed extrahepatic intra-abdominal tumor recurrence. CONCLUSIONS: The treatment strategy used in ARST0332 achieved favorable outcomes for patients with ESL despite a substantial proportion having high-risk disease features. Deferring tumor resection until after neoadjuvant chemotherapy may decrease the risk of intraoperative tumor rupture and improve the likelihood of adequate surgical margins.
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Neoplasias Hepáticas , Neoplasias de Células Germinales y Embrionarias , Sarcoma , Humanos , Femenino , Masculino , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Niño , Adolescente , Adulto Joven , Sarcoma/terapia , Sarcoma/patología , Adulto , Preescolar , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias de Células Germinales y Embrionarias/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Ifosfamida/administración & dosificación , Ifosfamida/uso terapéutico , LactanteRESUMEN
BACKGROUND: Previous studies have shown that neutrophil-to-lymphocyte (NLR) ratio at diagnosis and early lymphocytes recovery on doxorubicin-based chemotherapy, may impact the outcome in patients with osteosarcoma (OST). This study aimed to evaluate the prognostic value of hemogram parameters in patients with OST treated with high-dose methotrexate and etoposide/ifosfamide (M-EI) chemotherapy. MATERIALS AND METHODS: We retrospectively analyzed the prognostic value of various hemogram parameters at diagnosis and during therapy in a large consecutive cohort of patients with OST included in the French OS2006 trial and treated with M-EI chemotherapy. RESULTS: A total of 164 patients were analyzed. The median age was 14.7 years (interquartile range [IQR]: 11.7-17). Median follow-up was 5.6 years (IQR: 3.3-7.7 years). Three-year event-free survival (EFS) and overall survival (OS) were 71.5% (95% confidence interval [CI]: 64%-78%) and 86.4% (95% CI: 80%-91%), respectively. In univariate analysis, blood count parameters at diagnosis and early lymphocyte recovery at Day 14 were not found prognostic of survival outcomes. By contrast, an increase of NLR ratio at Day 1 of the first EI chemotherapy (NLR-W4) was associated with reduced OS in univariate (p = .0044) and multivariate analysis (hazards ratio [HR] = 1.3, 95% CI: 1.1-1.5; p = .002), although not with EFS. After adjustment on histological response and metastatic status, an increase of the ratio NLR-W4 of 1 was associated with an increased risk of death of 30%. CONCLUSIONS: We identified NLR-W4 as a potential early biomarker for survival in patients with OST treated with M-EI chemotherapy. Further studies are required to confirm the prognostic value of NLR and better identify immune mechanisms involved in disease surveillance.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Óseas , Etopósido , Metotrexato , Osteosarcoma , Humanos , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/mortalidad , Osteosarcoma/patología , Osteosarcoma/sangre , Femenino , Masculino , Adolescente , Estudios Retrospectivos , Niño , Pronóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Neoplasias Óseas/sangre , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Tasa de Supervivencia , Neutrófilos/patología , Estudios de Seguimiento , Linfocitos/patología , Ifosfamida/administración & dosificación , Francia/epidemiologíaRESUMEN
INTRODUCTION: NUT carcinoma (NC) is an underdiagnosed and aggressive poorly differentiated or squamous cell cancer. A subset of NC is sensitive to chemotherapy, but the optimal regimen is unknown. Experts have recommended platinum- and ifosfamide-based therapy based on case reports. METHODS: Patients with pathologically confirmed NC with known survival outcomes after chemotherapy and consented to participate in a worldwide registry were studied. Results were summarized using descriptive methods. RESULTS: The study included 118 patients with NC. Median age was 34 (range: 1-82) years, 39% were women, and 61% harbored a BRD4::NUTM1 fusion. Patients received platinum (74%) or ifosfamide (26%, including regimens with both, 13%). Of 62 patients with nonmetastatic disease, 40% had a thoracic primary. Compared with platinum-based chemotherapy, patients who received ifosfamide-based chemotherapy had nominally higher progression-free survival (12 mo: 59% [95% CI: 32-87] versus 37% [95% CI: 22-52], hazard ratio = 0.68 [0.32, 1.42], p = 0.3) but not overall survival (OS). Among the 56 patients with metastatic disease, 80% had a thoracic primary. Ifosfamide had an objective response rate (ORR) of 75% (six of eight) and platinum had an ORR of 31% (11 of 36). Nevertheless, there was no difference in progression-free survival or OS. The 3-year OS of the entire cohort was 19% (95% CI: 10%-28%). Of the 11 patients alive greater than 3 years, all presented with nonmetastatic and operable or resectable disease. CONCLUSION: There is a numerically higher ORR for ifosfamide-based therapy compared with platinum-based therapy, with limited durability. OS at 3 years is only 19%, and development of effective therapies is an urgent unmet need for this patient population.
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Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Anciano de 80 o más Años , Adulto Joven , Adolescente , Niño , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ifosfamida/administración & dosificación , Ifosfamida/uso terapéutico , Tasa de Supervivencia , Proteínas Nucleares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidadRESUMEN
BACKGROUND AND AIMS: Nuclear protein of the testis ( NUT ) carcinoma (NC) is a rare and highly aggressive tumor mainly occurring in adolescents and young adults, defined by the presence of a somatic NUTM1 rearrangement. The aim is to establish internationally harmonized consensus recommendations for the diagnosis and treatment of adolescents and young adults with NC in the framework of the European Reference Network for Paediatric Oncology. METHODS: The European Cooperative Study Group for Pediatric Rare Tumors developed recommendations according to the Consensus Conference Standard Operating procedure methodology and reviewed by external "experts." No evidence of level I to II exists. Recommendations were developed based on published prospective (level III), but more frequently retrospective series (level IV), case reports (level V), and personal expertise (level V). In addition, "strength" of recommendations were categorized by grading (grade A to E). RESULTS: Histology is mandatory for the diagnosis of NC, including immunolabeling with anti-NUT antibodies and molecular biology ( NUTM1 rearrangement) (level V; grade A). Treatment of NC usually combines aggressive approaches in multimodal regimens. Chemotherapy should be considered as first-line treatment (neoadjuvant vincristine-adriamycin-ifosfamide/cisplatin-adriamycin-ifsofamide or vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide) for unresectable or metastatic tumor (ie, 3 courses), rapidly followed by local treatment (level IV; grade B). Referral to a specialized surgical oncology center is highly recommended (level V; grade A). In localized NC, a complete microscopic surgical resection should be attempted whenever and as soon as possible, followed by primary irradiation (60 to 70 Gy) and involved lymph nodes area (level IV; grade B). For head and neck tumors, a systematic neck dissection might be considered, even if N0 (level V; grade C). Adjuvant postirradiation chemotherapy is recommended, for a total of 9 to 12 courses (level IV; grade B). For first-line resected tumors, concomitant adjuvant chemotherapy to radiotherapy may be discussed (level IV; grade B). Targeted therapies and immunotherapeutic regimens should be delivered in the setting of prospective trials (level V; grade B). CONCLUSIONS: This project leads to a consensus strategy based on international experience with this very rare disease.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma , Adolescente , Niño , Humanos , Masculino , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Carcinoma/genética , Carcinoma/patología , Cisplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Ifosfamida/administración & dosificación , Terapia Neoadyuvante , Estudios Prospectivos , Estudios Retrospectivos , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: Preoperative chemotherapy is widely applied to high-grade localized soft tissue sarcomas (STSs); however, the prognostic significance of histological response to chemotherapy remains controversial. This study aimed to standardize evaluation method of histological response to chemotherapy with high agreement score among pathologists, and to establish a cut-off value closely related to prognosis. METHODS: Using data and specimens from the patients who had registered in the Japan Clinical Oncology Group study, JCOG0304, a phase II trial evaluating the efficacy of perioperative chemotherapy with doxorubicin (DOX) and ifosfamide (IFO), we evaluated histological response to preoperative chemotherapy at the central review board. RESULTS: A total of 64 patients were eligible for this study. The percentage of viable tumor area ranged from 0.1% to 97.0%, with median value of 35.7%. Regarding concordance proportion between pathologists, the weighted kappa coefficient (κ) score in all patients was 0.71, indicating that the established evaluation method achieved substantial agreement score. When the cut-off value of the percentage of the residual tumor area was set as 25%, the p-value for the difference in overall survival showed the minimum value. Hazard ratio of the non-responder with percentage of the residual tumor < 25%, to the responder was 4.029 (95% confidence interval 0.893-18.188, p = 0.070). CONCLUSION: The standardized evaluation method of pathological response to preoperative chemotherapy showed a substantial agreement in the weighted κ score. The evaluation method established here was useful for estimating of the prognosis in STS patients who were administered perioperative chemotherapy with DOX and IFO. TRIAL REGISTRATION: UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia Adyuvante/estadística & datos numéricos , Monitoreo de Drogas/normas , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/terapia , Adulto , Anciano , Doxorrubicina/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Periodo Preoperatorio , Pronóstico , Estándares de Referencia , Valores de Referencia , Sarcoma/mortalidad , Sarcoma/patología , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
This study reports the treatment feasibility and efficacy of a novel multiagent intensive treatment program for young patients with desmoplastic small round cell tumor. This small series includes three patients and should be seen as a first suggestion of integration of the dose density and the maintenance chemotherapy concept. The IrIVA regimen (irinotecan, ifosfamide, vincristine, and actinomycin-D) is added-used at a short interval between chemotherapy administrations-at more classic intensive ifosfamide-based regimens. The vinorelbine and low-dose oral cyclophosphamide maintenance therapy is added at the end of conventional chemotherapy to achieve an antiangiogenic effect.
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Dactinomicina/administración & dosificación , Tumor Desmoplásico de Células Pequeñas Redondas/tratamiento farmacológico , Ifosfamida/administración & dosificación , Irinotecán/administración & dosificación , Vincristina/administración & dosificación , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Dactinomicina/efectos adversos , Tumor Desmoplásico de Células Pequeñas Redondas/patología , Tumor Desmoplásico de Células Pequeñas Redondas/cirugía , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Humanos , Ifosfamida/efectos adversos , Irinotecán/efectos adversos , Masculino , Resultado del Tratamiento , Vincristina/efectos adversos , Vinorelbina/administración & dosificación , Vinorelbina/efectos adversos , Adulto JovenRESUMEN
Peripheral T-cell lymphoma (PTCL) is an aggressive tumor, rarely seen in pediatrics or adolescent and young adults (AYAs) so there is no upfront or relapsed standard of care. The authors describe a 16-year-old with PTCL, treated with chemotherapy and autologous stem cell transplant. Upon relapse, he received ifosfamide, carboplatin, etoposide, and radiation with durable remission of 4 years. Data in pediatric/AYA PCTL continue to lack an understanding of the biology and microenvironment, the differences to adult patients, and a lack of adequate therapy. Targeted therapy may improve outcomes for children and AYAs with refractory or relapsed PTCL.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células T Periférico/terapia , Trasplante de Células Madre , Adolescente , Autoinjertos , Carboplatino/administración & dosificación , Etopósido/administración & dosificación , Humanos , Ifosfamida/administración & dosificación , Masculino , RecurrenciaRESUMEN
BACKGROUND: Uterine carcinosarcoma (UCS) is a rare but highly lethal disease. Adjuvant chemotherapy is highly recommended for advanced UCS. To date, the standard chemotherapy regimen is still uncertain, although two regimens as paclitaxel-platinum (PP) and ifosfamide-platinum (IP) regimens are most commonly used. The aims of the current study attempt to compare both regimens in the management of advanced UCS patients. METHODS: We evaluated advanced UCS patients who were treated either with PP or with IP after primary cytoreductive surgery in single institute retrospectively. The clinical-pathological parameters, recurrence, and survival were recorded. RESULTS: A total of 16 patients were analyzed. Twelve patients received adjuvant PP therapy, and the remaining four patients received IP therapy. The median follow-up time was 28 months, ranging from 3.8 months to 121 months. Disease-related death occurred in 10 patients (62.5%). The median progression-free survival was 4.9 months, ranging from 3.8 months to 36.5 months in IP, and 23.1 months, ranging from 9.3 months to 121 months in PP, with statistically significant difference (p = 0.04). The median overall survival was 9.5 months (ranging from 3.8 months to 36.5 months) and 28.7 months (ranging from 10.3 months to 121 months) in IP and PP, respectively, without statistically significant difference (p = 0.06). Presence of pelvic and para-aortic lymphadenopathy and deep myometrial invasion (>1/2) were associated with worse prognosis by univariate analysis. No prognostic factor could be identified using multivariate analysis model. CONCLUSION: In the current study, due to extremely little number of subjects enrolled, the advantage of using paclitaxel-platinum regimen in the management of advanced UCS was still unclear, although a certain trend of favoring was supposed. We are looking forward to seeing more studies to identify the approximate regimen in the management of this highly lethal disease.
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Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Ifosfamida/administración & dosificación , Paclitaxel/administración & dosificación , Platino (Metal)/administración & dosificación , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Periodo Posoperatorio , Estudios RetrospectivosRESUMEN
RATIONALE: Synovial sarcoma is a rare malignant tumor that typically originates from the soft tissue of the extremities. The occurrence of primary pharyngeal synovial sarcoma is even rarer, and few studies have reported its radiological features. Here, we report a case of pediatric primary pharyngeal synovial sarcoma and describe the conventional and advanced magnetic resonance imaging (MRI) findings with pathologic correlation. PATIENT CONCERNS: An 11-year-old girl presented to the otolaryngologic clinic with dysphagia. DIAGNOSIS: Laryngoscopy revealed a large mass in the oropharynx. MRI revealed a well-defined soft tissue mass with a maximal diameter of approximately 5âcm originating from the submucosal space of the oropharynx. The mass was primarily solid and showed homogeneous contrast-enhancement. The mass was hypointense on T1-weighted images and hyperintense on T2-weighted images. The mass showed a homogeneously low apparent diffusion coefficient value on diffusion-weighted imaging, which indicated high tumor cellularity. Dynamic contrast-enhanced MRI revealed a hypovascular tumor with low values of the volume transfer constant between the extracellular extravascular space and blood plasma and blood plasma volume per unit tissue volume. Amide proton transfer-weighted MRI revealed a relatively high amide proton transfer signal in the tumor, indicating a high protein/peptide component. The patient underwent partial surgical resection of the tumor, and the diagnosis of biphasic synovial sarcoma was confirmed on postoperative pathological examination. INTERVENTION: The patient was started on chemotherapy with vincristine, ifosfamide, doxorubicin, and etoposide. OUTCOMES: The tumor did not respond to the 3 cycles of the chemotherapy. Thus, the patient underwent second surgery and subsequent radiation therapy. The patient is now under ifosfamide/carboplatin/etoposide chemotherapy. LESSON: Synovial sarcoma should be considered in the differential diagnosis of pediatric oropharyngeal submucosal tumors. Multimodal MRI may aid diagnosis, although the final diagnosis should be based on the postoperative pathological examination findings.