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BACKGROUND: We aimed at investigating outcome of systemic treatments in advanced breast PT. METHODS: All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the referral sarcoma centers involved in the study, were retrospectively reviewed. RESULTS: 56 female patients were identified. Median age was 52 (range of 25-76) years. Patients received a median number of 2 systemic treatments (range of 1-4). Best responses according to RECIST were 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with high-dose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were 5.7 (IQR 2.5-9.1) months with AI; 3.2 (IQR 2.2-5.0) months with anthracycline alone; 3.4 (IQR 1.4-6.7) months with HD-IFX; 2.1 (IQR 1.4-5.2) months with gemcitabine-based chemotherapy; 1.8 (IQR 0.7-6.6) months with trabectedin; 3.4 (IQR 3.1-3.8) months with TKI. With a median follow-up of 35.3 (IQR 17.6-66.9) months, OS from the start of first-line systemic treatment was 15.2 (IQR 7.6-39.6) months. CONCLUSION: In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however, with a median PFS of 5.7 months. Other systemic treatments were poorly active.
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Neoplasias de la Mama , Sarcoma , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Persona de Mediana Edad , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios Retrospectivos , Sarcoma/patologíaRESUMEN
BACKGROUND: In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery in localized, high/intermediate-risk gastrointestinal stromal tumors (GIST) patients. Interim analysis results were published in 2015 upon recommendation from an independent data review committee. We report the final outcome of the study. PATIENTS AND METHODS: This was a randomized, open-label, multicenter phase III trial carried out at 112 hospitals in 12 countries. Patients were randomized to 2 years of imatinib, 400 mg daily, or no further therapy after surgery. The primary endpoint was imatinib failure-free survival (IFFS), while relapse-free survival (RFS), relapse-free interval (RFI), overall survival (OS) and toxicity were secondary endpoints. Adjusting for the interim analyses, results on IFFS were assessed on a 4.3% significance level; for the other endpoints, 5% was used. RESULTS: Nine hundred and eight patients were randomized between January 2005 and October 2008: 454 to imatinib and 454 to observation; 835 patients were eligible. With a median follow-up of 9.1 years, 5 (10)-year IFFS was 87% (75%) in the imatinib arm versus 83% (74%) in the control arm [hazard ratio (HR) = 0.87, 95.7% confidence interval (CI) (0.65; 1.15), P = 0.31]; RFS was 70% versus 63% at 5 years and 63% versus 61% at 10 years, [HR = 0.71, 95% CI (0.57; 0.89), P = 0.002]; OS was 93% versus 92% at 5 years and 80% versus 78% at 10 years [HR = 0.88, 95% CI (0.65; 1.21), P = 0.43]. Among 526 patients with high-risk GIST by local pathology, 10-year IFFS and RFS were 69% versus 61%, and 48% versus 43%, respectively. CONCLUSIONS: With 9.1 years of follow-up, a trend toward better long-term IFFS in imatinib-treated patients was observed in the high-risk subgroup. Although the difference was not statistically significant and the surrogacy value of such an endpoint is not validated, this may be seen as supporting the results reported by the Scandinavian/German trial, showing a sustained small but significant long-term OS benefit in high-risk GIST patients treated with 3 years of adjuvant imatinib.
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Antineoplásicos , Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Sarcoma , Antineoplásicos/uso terapéutico , Quimioterapia Adyuvante , Neoplasias Gastrointestinales/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Humanos , Mesilato de Imatinib/uso terapéutico , Italia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Sarcoma/tratamiento farmacológicoAsunto(s)
Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Sarcoma , Estudios de Seguimiento , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/epidemiología , Neoplasias Gastrointestinales/terapia , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/epidemiología , Tumores del Estroma Gastrointestinal/terapia , Humanos , Sarcoma/terapiaRESUMEN
BACKGROUND: This study was designed to assess patterns of recurrence and long-term outcomes of patients undergoing surgery for localized retroperitoneal sarcoma (RPS) after neoadjuvant high dose long-infusion ifosfamide (HLI) and radiotherapy (RT). METHODS: Patients received three cycles of HLI (14 g/m2). RT was started in combination with II cycle up to a total dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the end of RT. The primary endpoint was relapse-free survival (RFS) after surgery. Secondary endpoints were overall survival (OS), crude cumulative incidence of local recurrence (CCI-LR), and distant metastases (CCI-DM). For patients who relapsed, progression-free survival (PFS) and post-relapse OS were estimated. The trial was registered with ITASARC_*II_2004_003. RESULTS: Between 2003 and 2010, 83 patients were recruited. At a median follow-up of 91.7 months, 42 (56%) of 75 operated patients developed LR (n = 27) or DM (n = 10) or both LR and DM (n = 5) relapse. Seven-year RFS was 46.6% [95% confidence interval (CI) 29.6-52.4]. Thirty-two patients died. Seven-year OS rate was 63.2% (95% CI 42.7-66.0). The corresponding CCI of LR and DM were 37.4% [standard error (SE) 5.5%] and 20.0% (SE 12.6%), respectively. The only factor significantly associated with LR was FNCLCC grading, whereas histological subtype resulted associated with DM. At recurrence, 24 patients (57%) underwent surgery. Two-year post-relapse PFS and OS rates for patients developing LR or DM were 14.8, 41.0, 27.3, and 63.6%, respectively. CONCLUSIONS: LR after neoadjuvant CT-RT for RPS were predominantly infield. While almost one half of relapsed patients underwent further surgery, prognosis was poor.
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Quimioradioterapia , Ifosfamida/uso terapéutico , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Neoplasias Retroperitoneales/patología , Sarcoma/patología , Adulto , Anciano , Antineoplásicos Alquilantes/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/terapia , Pronóstico , Neoplasias Retroperitoneales/terapia , Sarcoma/terapia , Tasa de SupervivenciaRESUMEN
BACKGROUND: To report on long-term results of a phase 3 trial comparing three versus five cycles of adjuvant chemotherapy (CT) with full-dose epirubicin+ifosfamide in high-risk soft tissue sarcomas (STS). METHODS: Patients (pts) were randomized to receive three preoperative cycles of epirubicin 120 mg/m2 and ifosfamide 9 g/m2 (Arm A) or to receive the same three preoperative cycles plus two postoperative cycles (Arm B). Radiotherapy could be either delivered in the preoperative or in the postoperative setting. Non-inferiority of the primary end point, OS, was assessed by the confidence interval of the hazard ratio (HR; Arm A/Arm B) derived from Cox model. RESULTS: Between January 2002 and April 2007, 164 pts were assigned to arm A and 164 to arm B. At a median follow-up (FU) of 117 months (IQ range 103-135 months), 123 deaths were recorded: 58 in Arm A and 65 in Arm B. Ten-year OS was 61% for the entire group of patients: 64% in Arm A and 59% in Arm B. The intention-to-treat analysis confirmed that three cycles were not inferior to five cycles (one-sided 95% upper confidence limit was 1.24). A per protocol analysis was consistent with these results. Pts with leiomyosarcoma and undifferentiated pleomorphic sarcoma (UPS) had the lowest, and the highest response rates, respectively. Consistently, Leiomyosarcoma and UPS had the worse and the best prognosis, respectively. CONCLUSIONS: At a longer FU, the non-inferiority of three cycles of a full-dose conventional CT in comparison to five is confirmed. Response to therapy is also confirmed to be associated with better survival. This regimen is currently tested within an ongoing international trial against three cycles of a neoadjuvant histology-tailored CT (ClinicalTrials.gov Identifier: NCT01710176).
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Quimioterapia Adyuvante , Leiomiosarcoma/tratamiento farmacológico , Pronóstico , Sarcoma/tratamiento farmacológico , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leiomiosarcoma/patología , Leiomiosarcoma/radioterapia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Sarcoma/patología , Sarcoma/radioterapia , Resultado del TratamientoRESUMEN
While they account for one-fifth of new cancer cases, rare cancers are difficult to study. A higher than average degree of uncertainty should be accommodated for clinical as well as for population-based decision making. Rules of rational decision making in conditions of uncertainty should be rigorously followed and would need widely informative clinical trials. In principle, any piece of new evidence would need to be exploited in rare cancers. Methodologies to explicitly weigh and combine all the available evidence should be refined, and the Bayesian logic can be instrumental to this end. Likewise, Bayesian-design trials may help optimize the low number of patients liable to be enrolled in clinical studies on rare cancers, as well as adaptive trials in general, with their inherent potential of flexibility when properly applied. While clinical studies are the mainstay to test hypotheses, the potential of electronic patient records should be exploited to generate new hypotheses, to create external controls for future studies (when internal controls are unpractical), to study effectiveness of new treatments in real conditions. Framework study protocols in specific rare cancers to sequentially test sets of new agents, as from the early post-phase I development stage, should be encouraged. Also the compassionate and the off-label settings should be exploited to generate new evidence, and flexible regulatory innovations such as adaptive licensing could convey new agents early to rare cancer patients, while generating evidence. Though validation of surrogate end points is problematic in rare cancers, the use of an updated notion of tumor response may be of great value in the single patient to optimize the use of therapies, all the more the new ones. Disease-based communities, involving clinicians and patients, should be regularly consulted by regulatory bodies when setting their policies on drug approval and reimbursement in specific rare cancers.
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Estudios Clínicos como Asunto/métodos , Neoplasias , Enfermedades Raras , Proyectos de Investigación , HumanosRESUMEN
BACKGROUND: The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). METHODS: We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. RESULTS: Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. CONCLUSION: Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities.
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Determinación de Punto Final/normas , Tumores del Estroma Gastrointestinal/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Proyectos de Investigación/normas , Sarcoma/terapia , Terminología como Asunto , Consenso , Técnica Delphi , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Determinación de Punto Final/clasificación , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/mortalidad , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/clasificación , Sarcoma/diagnóstico , Sarcoma/mortalidad , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
BACKGROUND: More than 60 per cent of patients treated surgically for primary retroperitoneal sarcoma survive for at least 5 years. Extended surgical resection has been proposed for primary disease, but long-term morbidity data are lacking. A cross-sectional study was conducted to assess the long-term morbidity of patients undergoing surgery for retroperitoneal sarcoma. METHODS: Patients operated on between January 2002 and December 2011 were eligible for the study. Long-term morbidity was evaluated based on a semistructured clinical interview. Lower limb function was assessed by means of the Lower Extremity Functional Scale (LEFS), a self-report questionnaire with a total score ranging from 0 (low functioning) to 80 (high functioning). Pain was investigated by means of the Brief Pain Inventory--Short Form, with pain intensity scores reported on a scale from 0 (no pain) to 10 (worst pain). RESULTS: Some 243 patients underwent surgery, and 101 of 160 patients who were alive at the time of the investigation responded to the study invitation letter. Finally, 95 patients were enrolled in the study. Sensory impairment of the limbs was reported in 72 patients (76 per cent). The median LEFS score was 60 (i.q.r. 43-73). Mean scores for the pain intensity items varied from 1.23 to 2.68. In multivariable analysis, there was no difference in median levels of creatinine at survey between patients who did or did not undergo nephrectomy (difference between median values 13 (95 per cent c.i. -4 to 30) µmol/l; P = 0.170). CONCLUSION: Severe chronic pain and lower limb motor impairment after multivisceral resection for retroperitoneal sarcomas are rare. Long-term renal function is not significantly impaired when nephrectomy is performed.
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Complicaciones Posoperatorias/epidemiología , Neoplasias Retroperitoneales/cirugía , Sarcoma/cirugía , Adulto , Dolor Crónico/diagnóstico , Dolor Crónico/epidemiología , Dolor Crónico/etiología , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/epidemiología , Complicaciones Posoperatorias/diagnóstico , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Host immunity is emerging as a key player in the prognosis and response to treatment of cancer patients. However, the impact of the immune system and its modulation by therapies are unknown in rare soft tissue sarcomas such as solitary fibrous tumours (SFTs), whose management in the advanced forms includes anti-angiogenic therapy. Here, we studied the in situ and systemic immune status of advanced SFT patients and the effects of sunitinib malate (SM) in association with the clinical efficacy. METHODS: Immune contexture of SFTs was assessed by immunohistochemistry in lesions from untreated or SM-treated patients. Frequency of circulating myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and T-cell functions was assessed ex vivo in SFT patients prior and during anti-angiogenic therapy. Patients with long-term tumour control were included to correlate immune profiles and clinical responses. RESULTS: Anti-angiogenic naïve SFT lesions were heavily infiltrated by CD163(+)CD14(+)CD68(-) and CD163(+)CD14(-)CD68(-) myeloid cells but devoid of T cells. Conversely, post-SM tumours acquired a new subset of CD68(+)CD14(+) myeloid cells and displayed traits of an on-going adaptive immunity, strongly enriched in activated CD8(+) and CD4(+) T cells. These changes at the tumour site paralleled the alleviation of systemic immunosuppression and the drop in the frequency of circulating monocytic MDSCs (mMDSCs) and granulocytic MDSCs (gMDSCs). Rebound in the number of mMDSCs, but not of gMDSCs occurred at disease progression, and a reduced percentages of mMDSCs, comparable to those found in healthy donors (HDs), endured only in the SM-responsive patients. CONCLUSIONS: The immune contexture of SFT patients is heavily involved in anti-angiogenic therapy and it could be exploited to achieve more durable disease control through immune-based combination strategies.
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Inmunidad Adaptativa/efectos de los fármacos , Inhibidores de la Angiogénesis/farmacología , Indoles/farmacología , Células Progenitoras Mieloides/inmunología , Pirroles/farmacología , Tumores Fibrosos Solitarios/inmunología , Adulto , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Terapia de Inmunosupresión , Indoles/uso terapéutico , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Células Progenitoras Mieloides/efectos de los fármacos , Pirroles/uso terapéutico , Tumores Fibrosos Solitarios/sangre , Tumores Fibrosos Solitarios/tratamiento farmacológico , Sunitinib , Resultado del Tratamiento , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunologíaRESUMEN
Desmoid-type fibromatosis (DF) is a rare locally aggressive monoclonal proliferation of myofibroblasts lacking metastatic capacity. It may be observed in nearly every part of the body. Considering the variable clinical presentations, anatomic locations, and biologic behaviors, an individualized treatment approach is required. The pathogenesis of DF is not completely understood even if a high prevalence (â¼85%) of CTNNB1 mutations discovered in sporadic DF underlies the importance of the Wnt/ß-catenin pathway. No established and evidence-based approach for the treatment of this neoplasm is available as of today. Considering the unpredictable behavior and the heterogeneity of this disease, we propose a treatment algorithm approved by the French and the Italian Sarcoma Group, based on a front-line wait and see approach and subsequent therapy in the case of progression. A careful counseling at a referral center is mandatory and should be offered to all patients affected by sporadic DF from the time of their diagnosis.
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Fibromatosis Agresiva/radioterapia , Fibromatosis Agresiva/cirugía , Espera Vigilante , beta Catenina/genética , Fibromatosis Agresiva/genética , Francia , Humanos , Italia , Recurrencia Local de Neoplasia/radioterapia , Vía de Señalización Wnt/genéticaRESUMEN
The number of cancer patients in Europe is rising and significant advances in basic and applied cancer research are making the provision of optimal care more challenging. The concept of cancer as a systemic, highly heterogeneous and complex disease has increased the awareness that quality cancer care should be provided by a multidisciplinary team (MDT) of highly qualified healthcare professionals. Cancer patients also have the right to benefit from medical progress by receiving optimal treatment from adequately trained and highly skilled medical professionals. Built on the highest standards of professional training and continuing medical education, medical oncology is recognised as an independent medical specialty in many European countries. Medical oncology is a core member of the MDT and offers cancer patients a comprehensive and systemic approach to treatment and care, while ensuring evidence-based, safe and cost-effective use of cancer drugs and preserving the quality of life of cancer patients through the entire 'cancer journey'. Medical oncologists are also engaged in clinical and translational research to promote innovation and new therapies and they contribute to cancer diagnosis, prevention and research, making a difference for patients in a dynamic, stimulating professional environment. Medical oncologists play an important role in shaping the future of healthcare through innovation and are also actively involved at the political level to ensure a maximum contribution of the profession to Society and to tackle future challenges. This position paper summarises the multifarious and vital contributions of medical oncology and medical oncologists to today's and tomorrow's professional cancer care.
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Oncología Médica/educación , Neoplasias/terapia , Rol del Médico , Europa (Continente) , Medicina Basada en la Evidencia , Humanos , Comunicación Interdisciplinaria , Oncología Médica/normas , Neoplasias/diagnóstico , Relaciones Médico-Paciente , Calidad de la Atención de SaludRESUMEN
BACKGROUND: This is a multicentre, single-arm, phase II study aimed at further exploring the activity of trabectedin as second-/further-line treatment in retroperitoneal leiomyosarcoma (LMS) and well-differentiated/dedifferentiated liposarcoma (LPS). MATERIALS AND METHODS: The primary endpoint was the growth modulation index (GMI) defined as the ratio between PFS under trabectedin (PFS) and during previous chemotherapy treatment: time to progression (TTP-1). Secondary endpoints were objective response rate (ORR) and PFS. As per protocol, patients were considered responders if the GMI was >1.33, non-responders if <0.75 and neither if 0.76-1.32. RESULTS: Overall 91 patients were assessable for the primary endpoint (32 patients with LMS and 59 patients with LPS): the median number of cycles received was 6.0 (Q1-Q3 3.0-12.0), and the main reason for treatment discontinuation was disease progression in 72% of patients. The median PFS was 6.0 months, while the median TTP1 was 7.5 months (8.1 and 6.4 months for LMS and LPS, respectively). Thirty-three patients [52%, 95% confidence interval (CI) 36% to 58%, P = 0.674, odds of response 1.1] had a GMI >1.33 (LMS 46%, 95% CI 26% to 67%, odds of response 0.85; LPS 56%, 95% CI 40% to 72%, odds of response 1.3). Overall, in LPS we observed 15/47 patients with a GMI <0.5 and 15/47 patients with a GMI >2. Among LMS patients, 9/26 had a GMI <0.5 and 10/26 had a GMI >2. Overall, ORR (complete response + partial response) was 16% (24% for LMS and 12% for LPS). CONCLUSIONS: While the primary endpoint of the study was not met, we noticed a subgroup of patients with a markedly discrepant TTP with trabectedin in comparison to previous therapy (GMI <0.5 or >2, the latter including some patients with a long TTP with trabectedin). A mismatch between PFS and overall survival was observed, possibly due to the natural history of the two different histologies and the availability of further lines in LMS.
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BACKGROUND: We report on a series of consecutive patients with localized radiation-associated angiosarcoma (RAAS) of the breast region (BR) treated at two Italian sarcoma reference centers. MATERIALS AND METHODS: We retrospectively reviewed all cases of primary, localized, resectable RAAS of the BR, treated at one of the two participating institutions from 2000 to 2019. Relapse-free survival (RFS) and overall survival (OS) were calculated. The prognostic role of several variables was investigated. A propensity score matched (PSM) analysis was carried out. RESULTS: Eighty-four patients were retrospectively identified. Nineteen out of 84 patients (22.6%) were pretreated with an anthracycline-based regimen for previous cancer. All patients but one underwent surgery, with 37/84 (44.1%) receiving surgery alone and 46/84 (54.8%) a multimodal approach: 18/84 (21.4%) received radiation therapy (RT) and 46/84 (54.9%) received chemotherapy. An anthracycline-based regimen was used in 10/84 patients (11.9%), while a gemcitabine-based regimen was used in 33/84 (39.3%). With a median follow-up of 51 months (interquartile range: 30-126 months), 36/84 patients (42.9%) relapsed and 35/84 patients (41.7%) died (8/84, 9.5% in the lack of metastatic disease). Five-year OS and 5-year RFS were 57% [95% confidence interval (CI) 43% to 68%] and 52% (95% CI 39% to 63%), respectively. Both (neo)adjuvant RT and chemotherapy were associated with better RFS [hazard ratio (HR) 0.25, 95% CI 0.08-0.83; HR 0.45, 95% CI 0.23-0.89] with a trend towards a better OS (HR 0.51, 95% CI 0.18-1.46; HR 0.60, 95% CI 0.29-1.24). Gemcitabine-based regimens seemed to perform better (HR 4.28, 95% CI 1.29-14.14). PSM analysis retained the above results. CONCLUSIONS: This retrospective study supports the use of (neo)adjuvant RT and chemotherapy, in primary, localized resectable RAAS of the BR. An effort to prospectively validate the role of (neo)adjuvant RT and chemotherapy is warranted.
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Neoplasias de la Mama , Hemangiosarcoma , Neoplasias Inducidas por Radiación , Humanos , Hemangiosarcoma/etiología , Hemangiosarcoma/terapia , Hemangiosarcoma/tratamiento farmacológico , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Anciano , Neoplasias Inducidas por Radiación/etiología , Adulto , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
BACKGROUND: To report on a prospective, investigator-driven, phase II study on lapatinib in epidermal growth factor receptor (EGFR)-positive advanced chordoma patients. PATIENTS AND METHODS: From December 2009 to January 2012, 18 advanced progressing chordoma patients entered this study (median age: 61 years; disease extent: metastatic 72% and locally advanced 28%). Epidermal growth factor receptor (EGFR) expression and activation were evaluated by immunohistochemistry and/or phospho-arrays, real-time polimerase chain reaction, fluorescence immunostaining. Fluorescence in situ hybridization analysis was also carried out. Patients received lapatinib 1500 mg/day (mean dose intensity = 1282 mg/day), until progression or toxicity. The primary study end point was response rate (RR) as per Choi criteria. Secondary end points were RR by Response Evaluation Criteria in Solid Tumor (RECIST), overall survival, progression-free survival (PFS) and clinical benefit rate (CBR; RECIST complete response + partial response (PR) + stable disease (SD) ≥ 6 months). RESULTS: All patients were evaluable for response. Six (33.3%) patients had PR and 7 (38.9%) SD, as their best Choi responses, corresponding to RECIST SD in all cases. Median PFS by Choi was 6 [interquartile (IQ) range 3-8] months. Median PFS by RECIST was 8 (IQ range 4-12) months, with a 22% CBR. CONCLUSIONS: This phase II study showed a modest antitumor activity of lapatinib in chordoma. The clinical exploitation of EGFR targeting in chordoma needs to be further investigated, both clinically and preclinically. Clinical trial Registration No: EU Clinical Trials Register trial no. 2009-014456-29.
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Antineoplásicos/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Cordoma/tratamiento farmacológico , Receptores ErbB/metabolismo , Quinazolinas/administración & dosificación , Adulto , Anciano , Antineoplásicos/efectos adversos , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Cordoma/mortalidad , Cordoma/secundario , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Lapatinib , Masculino , Persona de Mediana Edad , Quinazolinas/efectos adversos , Sacro/patología , Base del Cráneo/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Head and neck soft tissue sarcomas (STS) represent a rare disease. PATIENTS AND METHODS: One hundred and sixty-seven patients underwent surgery at our institution with an eradicating intent between 1990 and 2010. Local recurrence (LR), distant metastasis (DM) and disease-specific mortality (DSM) incidence were studied along with clinicopathological prognostic factors. RESULTS: Ten-year crude cumulative incidence (CCI) of LR, DM and DSM were 19%, 11% and 26%, respectively (median follow-up 66 months). Independent prognostic factors for DSM were tumor size (P < 0.001) and grade (P = 0.032), while surgical margins obtained a border-line significance (0.070); LR was affected by the tumor size (P = 0.001), while DM only by grade (P = 0.047). The median survival after LR and DM were 14 months and 7 months, respectively. Tumors sited in the paranasal sinus and supraclavicular region had the worst survival. CONCLUSIONS: Head and neck represent a very critical anatomical site for STS. Achievement of local disease control appears to be crucial, since even LR could be a life-threatening event.
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Neoplasias de Cabeza y Cuello/mortalidad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/mortalidad , Sarcoma/mortalidad , Supervivencia sin Enfermedad , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos , Sarcoma/radioterapia , Sarcoma/cirugía , Sobrevida , Resultado del TratamientoRESUMEN
BACKGROUND: To explore correlation between the quality of surgery and outcome in high-risk soft tissue sarcoma (STS) patients treated within a phase III randomized trial. PATIENTS AND METHODS: In the trial, all patients received three cycles of preoperative chemotherapy (CT) with epirubicin 120 mg/m(2) and ifosfamide 9 g/m(2) and were randomly assigned to receive two further postoperative cycles. Radiotherapy (RT) could be delivered in the preoperative or postoperative setting. The association between surgical margins and overall survival (OS) was studied in a univariate and multivariate fashion. RESULTS: Two hundred and fifty-two patients completed the whole treatment and were operated conservatively. At a median follow-up of 60 months (IQR, 45-74 months), the 5-year OS was 0.73, even in patients with positive and negative margins. The 5-year cumulative incidence (CI) of local recurrence (LR) in patients with positive and negative microscopic margins was 0.17 (standard error, SE, 0.08) and 0.03 (SE, 0.01), respectively. In the subgroup of patients receiving combined preoperative CT-RT and with positive surgical margins, the CI of LR was 0. CONCLUSIONS: In this setting of high-risk STS treated by preoperative CT or CT-RT, the negative impact of positive margins on the outcome was limited. When close margins can be anticipated preoperative CT-RT may be a reasonable option to maximize the chance of cure.