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1.
Medicine (Baltimore) ; 99(42): e22706, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080721

RESUMO

RATIONALE: Synovial sarcoma (SS) is a malignant neoplasm that arises from soft tissues proximal to the joints. It occurs primarily at the major joints of the extremities, but may also occur in the deep soft tissues around the joints. While primary renal synovial sarcoma (PRSS) is extremely rare, it is important to have a better understanding of their imaging and clinical features to establish an effective treatment plan. Correct identification of PRSS is also useful for treating renal neoplasms. PATIENT'S CONCERNS: A 56-year-old Chinese man was admitted to our hospital due to moderate, paroxysmal left-sided loin pain. DIAGNOSIS: Renal enhanced computed tomography (CT) scanning showed a relatively hypovascular lesion with calcification in the left kidney. A radical nephrectomy was performed in the left kidney. Postoperative pathology indicated SS with necrosis. The immunohistochemical findings were as follows: 34ßE12 (Epithelium+), Bcl-2(+), CD99(+), CK-pan((Epithelium+), EMA(Epithelium+), Ki-67(+60%), and Vimentin(+), CD34(-). INTERVENTIONS: The patient underwent radical left nephrectomy with no complications. OUTCOMES: After discharge, a close review for 3 months showed no evidence of recurrence. LESSONS: PRSS should be considered for the differential diagnosis of renal hypovascular tumors. When problems arise in distinguishing renal hypovascular tumors, surgical pathology is helpful in the final diagnosis and further treatment of the disease.


Assuntos
Neoplasias Renais/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Sarcoma Sinovial/diagnóstico , Terapia Combinada , Diagnóstico Diferencial , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/terapia , Nefrectomia , Sarcoma Sinovial/diagnóstico por imagem , Sarcoma Sinovial/terapia , Tomografia Computadorizada por Raios X
2.
Urol Clin North Am ; 47(4): 457-467, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008496

RESUMO

Biochemically recurrent prostate cancer represents a stage of prostate cancer where conventional (continued on next page) computed tomography and technetium Tc 99m bone scan imaging are unable to detect disease after curative intervention despite rising prostate-specific antigen. There is no clear standard of care and no systemic therapy has been shown to improve survival. Immunotherapy-based treatments potentially are attractive options relative to androgen deprivation therapy due to the generally more favorable side-effect profile. Biochemically recurrent prostate cancer patients have a low tumor burden and likely lymph node-based disease, which may make them more likely to respond to immunotherapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Imunoterapia/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/patologia , Idoso , Terapia Combinada , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Seleção de Pacientes , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Medição de Risco , Papel (figurativo) , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
3.
Bull Cancer ; 107(10): 1006-1018, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32958220

RESUMO

Endometrial cancer is a common cancer in older women and is often associated with comorbidities. Management of metastatic disease and/or relapse requires a multidisciplinary approach. Recent advances in the understanding of oncogenesis and molecular classification of endometrial cancers offer new therapeutic perspectives. These first recommendations, established following the methodology of Nice-Saint-Paul recommendations for clinical practice (RPC), aims to integrate molecular advances in diagnostic and therapeutic management. In 2020, the histological diagnosis of endometrial cancer is based on morphology and immunohistochemistry, including at least p53, oestrogen and progesterone receptors. Deficiency in the DNA mismatch repair system (MMR) must be assessed in all advanced endometrial tumors for oncogenetic and theranostic purposes. It can be sought initially by an analysis in immunohistochemistry with the 4 markers (MLH1, MSH2, MSH6, PMS2). Medical treatment depends on histological type, presence of hormone receptors and patient's profile to refer to chemotherapy (carboplatin-paclitaxel) or hormone therapy (for example of the progestogen type); in the event of MMR-deficiency, immunotherapy trial is the best option. As part of overall management of advanced endometrial cancer, radiotherapy (and surgery in rare cases) must be discussed, in particular in the event of loco-regional only relapse or oligometastatic disease.


Assuntos
Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/terapia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Árvores de Decisões , Neoplasias do Endométrio/secundário , Feminino , Humanos
4.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(9): 896-903, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32927515

RESUMO

Objective: At present, the modified NIH classification commonly used in clinical practice is still insufficient for assessing the risk of postoperative recurrence in some patients with intermediate-high risk gastrointestinal stromal tumors (GIST). Through exploring risk factors for recurrence of intermediate-high risk GIST, this study establishes a predictive model for recurrence with more convenience and more precision in order to guide adjuvant therapy for intermediate-high risk GIST patients. Methods: A retrospective case-control study was carried out. Clinical and pathological data of 432 GIST patients who did not receive preoperative targeted treatment, underwent complete resection in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2005 to June 2018, and were diagnosed as intermediate- or high-risk based on modified NIH classification by postopertive pathology, were retrospectively analyzed. Cox regression model was used to idenitify independent risk factors of recurrence, and a recurrence risk scoring model was established. The receiver operating characteristic curve (ROC curve), consistency index (C-index) and calibration curve were used to evaluate the accuracy of the scoring model in predicting the recurrence of moderate-risk and high-risk GIST patients. Results: Among 432 GIST patients, 332 were diagnosed as high-risk and 100 as moderate-risk; 237 were males and 195 females with average age of (57.4±12.4) years. Of 432 patients, 211 cases (48.8%) had fibrinogen (FIB) >3.5 g/L; 85 cases (19.7%) had platelet to lymphocyte ratio (PLR)>272.5; 122 cases (28.2%) had neutrophil to lymphocyte ratio (NLR) > 4.2; 102 cases (23.6%) had systemic inflammatory reaction index (SIRI)> 2.7; 198 cases (45.8%) had tumor long diameter >8 cm and 108 cases (25.0%) had mitotic counts > 8/50 HPF. Cox multivariable analysis showed that FIB (HR=1.789, 95% CI: 1.058-3.027, P=0.030), PLR (HR=1.862, 95% CI: 1.067-3.249, P=0.029), SIRI (HR=1.790, 95% CI: 1.039-3.084, P=0.036), tumor long diameter (HR=1.970, 95% CI: 1.105-2.925, P=0.017) and mitotic counts (HR=2.187, 95% CI:1.211-3.950, P=0.009) were independent risk factors for recurrence in patients with middle-risk and high-risk GIST. These 5 factors were included in the risk scoring model, which was given a weight score of 58 points, 62 points, 58 points, 63 points, and 78 points, respectively. Patients with a total score of ≤ 78 points were classified as moderate-risk recurrence (group I), those of 78 to 136 points as high-risk recurrence (group II) and those of >136 points as very high-risk recurrence (group III). ROC curve showed that the area under the curve (AUC) of the scoring model was 0.730 and the C-index was 0.724 (95% CI:0.687-0.787). The calibration curves and the Kaplan-Meier curves of patients in the three groups revealed that this model had a good predictive accuracy. Conclusions: For intermediate-risk and high-risk GIST patients, the preoperative FIB >3.5 g/L, PLR > 272.5 and SIRI > 2.7 are independent risk factors of recurrence after surgery. The recurrence risk scoring model established by combining tumor long diameter, mitotic counts, FIB, PLR and SIRI can effectively predict the risk of postoperative recurrence and metastasis in moderate-risk and high-risk GIST patients.


Assuntos
Fibrinogênio/análise , Neoplasias Gastrointestinais/sangue , Tumores do Estroma Gastrointestinal/sangue , Inflamação/sangue , Recidiva Local de Neoplasia/sangue , Idoso , Estudos de Casos e Controles , Terapia Combinada , Feminino , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/terapia , Humanos , Inflamação/diagnóstico , Inflamação/patologia , Inflamação/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
5.
Jpn J Clin Oncol ; 50(10): 1089-1096, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32776100

RESUMO

Squamous cell carcinoma of the head and neck is characterized by an immunosuppressive environment and evades immune responses through multiple resistance mechanisms. A breakthrough in cancer immunotherapy employing immune checkpoint inhibitors has evolved into a number of clinical trials with antibodies against programmed cell death 1 (PD-1), its ligand PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for patients with squamous cell carcinoma of the head and neck. CheckMate141 and KEYNOTE-048 were practice-changing randomized phase 3 trials for patients with platinum-refractory and platinum-sensitive recurrent or metastatic squamous cell carcinoma of the head and neck, respectively. Furthermore, many combination therapies using anti-CTLA-4 inhibitors, tyrosine kinase inhibitors and immune accelerators are currently under investigation. Thus, the treatment strategy of recurrent or metastatic squamous cell carcinoma of the head and neck is becoming more heterogeneous and complicated in the new era of individualized medicine. Ongoing trials are investigating immunotherapeutic approaches in the curative setting for locoregionally advanced disease. This review article summarizes knowledge of the role of the immune system in the development and progression of squamous cell carcinoma of the head and neck, and provides a comprehensive overview on the development of immunotherapeutic approaches in both recurrent/metastatic and locoregionally advanced diseases.


Assuntos
Imunoterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Ensaios Clínicos como Assunto , Resistencia a Medicamentos Antineoplásicos , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
6.
BMC Surg ; 20(1): 173, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736545

RESUMO

BACKGROUND: Laryngeal rhabdomyosarcomas (RMSs) mainly occurred in children, while were extremely rare in adults. Consequently, less information was available to guide clinicians to manage adult RMSs in larynx. CASE PRESENTATION: A 42-year-old man presented with a 2-year history of gradually worsening hoarseness. Then, he underwent a surgery with suspension laryngoscope with initially being diagnosed as vocal cord cyst. Unexpectedly, the lesion was proved to be embryonal rhabdomyosarcoma (ERMS), pathologically. Next, he underwent chemoradiotherapy, while the tumor relapsed 18 months after the last treatment. Subsequently, a vertical hemilaryngectomy and a right selective neck dissection was performed, and the chemotherapy according to the anticancer drug sensitivity in vitro was arranged. Until the last check-up 18 months after chemotherapy, the patient did not display clinical or radiological signs of local recurrence and metastases. CONCLUSIONS: Misdiagnosis and missed diagnosis of laryngeal RMSs might appear when tumors presented as smooth protuberance. We reported the first case of laryngeal RMSs in an adult with the multidisciplinary strategy based on the chemosensitivity assay in vitro. Furthermore, a systematic review of the literature was also discussed, highlighting the initial diagnostic pitfalls and subsequent management problems that may occur with this uncommon tumor.


Assuntos
Neoplasias Laríngeas , Laringe , Recidiva Local de Neoplasia/terapia , Rabdomiossarcoma Embrionário , Adulto , Quimiorradioterapia , Terapia Combinada , Erros de Diagnóstico , Feminino , Humanos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/terapia , Laringectomia , Laringe/cirurgia , Masculino , Esvaziamento Cervical , Rabdomiossarcoma Embrionário/diagnóstico , Rabdomiossarcoma Embrionário/cirurgia , Rabdomiossarcoma Embrionário/terapia
7.
Surgery ; 168(5): 816-824, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32778411

RESUMO

BACKGROUND: The risk of recurrence after curative surgery for pancreatic neuroendocrine tumors is reported to be between 10% and 30%. Among the available locoregional and systemic treatments, there are no specific recommendations regarding the best option for treating recurrent disease. The aims of this study were to evaluate the pattern of recurrence after surgery performed with curative intent for nonfunctioning pancreatic neuroendocrine tumors and to analyze the impact of treatment on disease progression. METHODS: All patients submitted to curative surgery for sporadic, well-differentiated, nonfunctioning pancreatic neuroendocrine tumors at 2 Italian centers between 2001 and 2018, with evidence of disease recurrence during follow-up, were included (n = 46). RESULTS: The most frequent type of recurrence was distant metastases (n = 38, 83%), located in the liver in 100% of cases, whereas 8 patients (17%) had an isolated local recurrence. Therapy for first disease recurrence included both locoregional (n = 14) and systemic treatments (n = 32). A second disease recurrence/progression occurred in 28 patients (61%). Patients who underwent systemic treatment after the first disease recurrence had better progression-free survival (1-year progression-free survival 78%) compared with those submitted to a locoregional procedure (1-year progression-free survival 50%; P = .007). Independent predictors of shortened progression-free survival after the first disease recurrence were the type of treatment (locoregional, hazard ratio 4.452, P = .001), the presence of necrosis (hazard ratio 2.732, P = .022) and age (>60 year, hazard ratio 2.494, P = .040). CONCLUSION: Upfront locoregional treatment of the first recurrence of nonfunctioning pancreatic neuroendocrine tumors after curative surgery should be avoided in favor of systemic therapy.


Assuntos
Recidiva Local de Neoplasia/terapia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos
8.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(5): 438-444, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32842421

RESUMO

Presacral recurrent rectal cancer which involves the presacral fascia and/or sacral bone is one subtype of locally recurrent rectal cancer. Presacral recurrent rectal cancer is fixed posteriorly to the pelvis due to presacral fascial and/or sacral bone involvement, which makes treatment difficult. There is lack of standardized diagnosis, treatment and surgical methods of presacral recurrent rectal cancer. The purpose of this expert consensus is to improve the understanding of this condition among Chinese specialists, and to help standardizing the diagnosis and therapeutic strategies for presacral recurrent rectal cancer. There are 17 statements on diagnosis (clinical symptoms, imaging, endoscopy, tumor marker detection and pathological biopsy), treatment (radiotherapy, chemotherapy and surgery), follow-up and prognosis for presacral recurrent rectal cancer. It is emphasized that radical surgery with the evaluation of multidisciplinary team (MDT) is the core method for the treatment. The choice of surgical approach should be based on the anatomic characteristics of presacral recurrence. The controversial issues in this consensus requires to further high-quality clinical research.


Assuntos
Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Neoplasias Retais/diagnóstico , Neoplasias Retais/terapia , China , Consenso , Humanos , Reto/cirurgia , Sacro/cirurgia
9.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(5): 451-455, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32842423

RESUMO

Presacral recurrence, a special recurrence type in rectal cancer after surgical treatment, refers to recurrent cancer invading the presacral soft tissue or the bony structure of sacrum. It is also a major constituent of recurrent rectal cancer (15.63% to 41.67%). Reports show that presacral recurrence rate is about 2.8% to 4.8%, and it is associated with clinic staging, pathological type, surgical approach, (neo) adjuvant radiochemotherapy, tumor distance from the anus, positive circumferential margin, lymph node metastasis, and unilateral lateral lymph node dissection. CT and MRI are important for the detection of presacral recurrence. Presacral recurrence is always combined with local recurrence in other parts and distant organ metastasis. Therefore, we divide that into the following 3 types: 1) presacral recurrence with distant metastasis; 2) presacral recurrence with pelvic wall or lateral lymph node metastasis, or with recurrence of pelvic organs or anastomosis; and 3) simple presacral relapse. According to MDT evaluation. We adopt corresponding treatment scheme and surgical approach depending on the types mentioned above. When tumor recurred in the sacrum and located lower than S2/3 articular surface, then resection of recurrent tumor combined with sacrococcygeal should be the treatment of choice. For presacral recurrence with anterior invasion, combined total pelvic exenteration were available. For presacral recurrence with lateral pelvic wall invasion, internal iliac arteriovenous resection and lateral lymph node dissection and para-aortic lymph node dissection should be carried out. R0 resection may improve the 5-year overall survival rate of these patients.


Assuntos
Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retais/epidemiologia , Neoplasias Retais/cirurgia , Sacro/cirurgia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Sacro/patologia
10.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(5): 461-465, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32842425

RESUMO

Objective: To investigate the clinicopathological features and prognostic factors in patients with presacral recurrent rectal cancer (PRRC). Methods: PRRC was defined as recurrence of rectal cancer after radical surgery involving posteriorly the presacral soft tissue, the sacrum/coccyx, and/or sacral nerve root. The diagnosis is confirmed with clinical symptoms (pain of pelvis/back/lower limb, bloody stools, increased frequency of defecation, and abnormal secretions), physical examination of perineal or pelvic masses, radiological findings, colonoscopy with histopathological biopsy, and the evaluation by multi-disciplinary team (MDT). Inclusion criteria: (1) primary rectal cancer undergoing radical surgery without distant metastasis; (2) PRRC was diagnosed; (3) complete inpatient, outpatient and follow-up data. According to the above criteria, clinical data of 72 patients with PRRC in Peking University People's Hospital from January 2008 to December 2017 were retrospectively analyzed. The clinicopathological features and follow-up data were summarized. Cox proportional hazard models was used to analyze the prognostic factors of PRRC. Results: Among 72 patients, 45 were male and 27 were female with a male-to-female ratio of 1.7:1.0. The median age at recurrence was 58 (34 to 83) years and the median interval from surgery to recurrence was 2.0 (0.2 to 17.0) years. The main symptom was pain in 48.6% (35/72) of patients. In addition, gastrointestinal symptoms were found in 25.0% (18/72) of patients. The presacral recurrent sites were presacral fascia in 36 (50.0%) patients, lower sacrum (S3~S5 or coccyx) in 25 (34.7%) patients, and higher sacrum (S1~S2) in 11 (15.3%) patients. Forty-seven (65.3%) patients underwent radical surgery (abdominal resection, abdominoperineal resection, sacrectomy, abdominosacral resection), 12 (16.7%) underwent non-radical surgery (colostomy, cytoreductive surgery), and 13 (18.1%) did not undergo any surgery but only receive palliative chemoradiotherapy and nutritional support treatment. Thirty-three (45.8%) patients received radiotherapy and/or chemotherapy (oxaliplatin, 5-fluorouracil, capecitabine, irinotecan, etc.). All the patients received follow-up, and the median follow-up time was 19 (2 to 72) months. The median overall survival time was 14 (1 to 65) months. The 1- and 3-year overall survival rates were 67.1% and 32.0%, respectively. Univariate analysis showed that age at recurrence (P=0.031) and radical resection (P<0.001) were associated with prognosis. Multivariate analysis demonstrated that radical resection was independent factor of good prognosis (RR=0.140, 95%CI: 0.061-0.322, P<0.001). Conclusions: Patients tend to develop presacral recurrent rectal cancer within 2 years after primary surgery. The main symptom is pain. Patients undergoing radical resection have a relatively good prognosis.


Assuntos
Recidiva Local de Neoplasia/diagnóstico , Neoplasias Retais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Estudos Retrospectivos
11.
Breast Cancer Res ; 22(1): 76, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32665033

RESUMO

BACKGROUND: Early luminal breast cancer (BC) represents 70% of newly diagnosed BC cases. Among them, small (under 2 cm) BC without lymph node metastasis (classified as T1N0) have been rarely studied, as their prognosis is generally favorable. Nevertheless, up to 5% of luminal T1N0 BC patients relapse with distant metastases that ultimately prove fatal. The aim of our work was to identify the mechanisms involved in metastatic recurrence in these patients. METHODS: Our study addresses the role that autonomous and non-autonomous tumor cell features play with regard to distant recurrence in early luminal BC patients. We created a cohort of T1N0 luminal BC patients (tumors between 0.5-2 cm without lymph node metastasis) with metastatic recurrence ("cases") and corresponding "controls" (without relapse) matched 1:1 on main prognostic factors: age, grade, and proliferation. We deciphered different characteristics of cancer cells and their tumor micro-environment (TME) by deep analyses using immunohistochemistry. We performed in vitro functional assays and highlighted a new mechanism of cooperation between cancer cells and one particular subset of cancer-associated fibroblasts (CAF). RESULTS: We found that specific TME features are indicative of relapse in early luminal BC. Indeed, quantitative histological analyses reveal that "cases" are characterized by significant accumulation of a particular CAF subset (CAF-S1) and decrease in CD4+ T lymphocytes, without any other association with immune cells. In multivariate analysis, TME features, in particular CAF-S1 enrichment, remain significantly associated with recurrence, thereby demonstrating their clinical relevance. Finally, by performing functional analyses, we demonstrated that CAF-S1 pro-metastatic activity is mediated by the CDH11/osteoblast cadherin, consistent with bones being a major site of metastases in luminal BC patients. CONCLUSIONS: This study shows that distant recurrence in T1N0 BC is strongly associated with the presence of CAF-S1 fibroblasts. Moreover, we identify CDH11 as a key player in CAF-S1-mediated pro-metastatic activity. This is independent of tumor cells and represents a new prognostic factor. These results could assist clinicians in identifying luminal BC patients with high risk of relapse. Targeted therapies against CAF-S1 using anti-FAP antibody or CDH11-targeting compounds might help in preventing relapse for such patients with activated stroma.


Assuntos
Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Fibroblastos Associados a Câncer/imunologia , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/imunologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida , Microambiente Tumoral/imunologia
12.
Nat Commun ; 11(1): 3549, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669548

RESUMO

Refractory metastatic rhabdomyosarcoma is largely incurable. Here we analyze the response of a child with refractory bone marrow metastatic rhabdomyosarcoma to autologous HER2 CAR T cells. Three cycles of HER2 CAR T cells given after lymphodepleting chemotherapy induces remission which is consolidated with four more CAR T-cell infusions without lymphodepletion. Longitudinal immune-monitoring reveals remodeling of the T-cell receptor repertoire with immunodominant clones and serum autoantibodies reactive to oncogenic signaling pathway proteins. The disease relapses in the bone marrow at six months off-therapy. A second remission is achieved after one cycle of lymphodepletion and HER2 CAR T cells. Response consolidation with additional CAR T-cell infusions includes pembrolizumab to improve their efficacy. The patient described here is a participant in an ongoing phase I trial (NCT00902044; active, not recruiting), and is 20 months off T-cell infusions with no detectable disease at the time of this report.


Assuntos
Imunoterapia Adotiva/métodos , Neoplasias Musculares/terapia , Recidiva Local de Neoplasia/terapia , Receptor ErbB-2/imunologia , Rabdomiossarcoma/terapia , Linfócitos T/transplante , Biópsia , Medula Óssea/patologia , Criança , Ensaios Clínicos Fase I como Assunto , Humanos , Masculino , Neoplasias Musculares/imunologia , Neoplasias Musculares/patologia , Recidiva Local de Neoplasia/imunologia , Receptores de Antígenos Quiméricos/imunologia , Indução de Remissão/métodos , Rabdomiossarcoma/imunologia , Rabdomiossarcoma/secundário , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transplante Autólogo/métodos , Resultado do Tratamento
13.
Nat Commun ; 11(1): 3617, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32680998

RESUMO

Multiple myeloma (MM) progression is characterized by the seeding of cancer cells in different anatomic sites. To characterize this evolutionary process, we interrogated, by whole genome sequencing, 25 samples collected at autopsy from 4 patients with relapsed MM and an additional set of 125 whole exomes collected from 51 patients. Mutational signatures analysis showed how cytotoxic agents introduce hundreds of unique mutations in each surviving cancer cell, detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature. Thus, a unique, single-cell genomic barcode can link chemotherapy exposure to a discrete time window in a patient's life. We leveraged this concept to show that MM systemic seeding is accelerated at relapse and appears to be driven by the survival and subsequent expansion of a single myeloma cell following treatment with high-dose melphalan therapy and autologous stem cell transplant.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Evolução Clonal/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Progressão da Doença , Relação Dose-Resposta a Droga , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Mutação/efeitos dos fármacos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Análise de Célula Única , Análise Espaço-Temporal , Transplante Autólogo/efeitos adversos , Sequenciamento Completo do Genoma
14.
Anticancer Res ; 40(8): 4741-4748, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727800

RESUMO

BACKGROUND/AIM: We aimed to investigate the efficacy of immune-cell therapy in terms of the survival of patients with neuroendocrine carcinoma of the uterine cervix (NECC), which lacks standardized therapeutic approaches. PATIENTS AND METHODS: We identified 17 patients who were diagnosed as having NECC and treated with immune-cell therapy. The clinical characteristics of these patients were extracted from their records and their overall survival was measured. RESULTS: Of the 17 patients, two patients with early-stage NECC without recurrence and three patients with less than four treatments were excluded. The median survival times from the time of diagnosis and from the initial administration of immune-cell therapy were 49.7 and 24.4 months, respectively. The overall survival rates at 1, 2, and 5 years were 63.6%, 38.2%, and 25.5%, respectively. Long-term survival was observed in the patients with distant metastases. CONCLUSION: The preliminary results of this retrospective study suggested the potential efficacy of immune-cell therapy for NECC.


Assuntos
Carcinoma Neuroendócrino/imunologia , Carcinoma Neuroendócrino/terapia , Colo do Útero/patologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/terapia , Adulto , Carcinoma Neuroendócrino/patologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Feminino , Humanos , Imunoterapia Adotiva/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias/métodos , Prognóstico , Neoplasias do Colo do Útero/patologia
15.
Bull Cancer ; 107(5S): S35-S40, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32620205

RESUMO

Oligometastatic prostate cancer (PCa) is an intense area of research thanks to the development of novel PET tracers such as 18F-choline or 68Ga-PSMA. Several retrospective studies in patients with hormone-sensitive oligorecurrent PCa (usually up to 5 metastases with a controlled primary tumor) showed PSA response and a low toxicity profile of metastasis-directed therapies (MDT) such as Stereotactic Body Radiation Therapy (SBRT) or salvage lymph node dissection. More recently, randomized phase 2 studies showed that SBRT can delay the introduction of androgen deprivation, decrease biochemical relapses and increase overall survival. Regarding oligoprogressive metastatic castration-resistant PCa, limited data is however available. Based on these studies the European Association of Urology and the American Society of Radiotherapy EAU now recommend using MDT instead of observation. Several studies are undergoing in France and worldwide in order to confirm the exact role of MDT.


Assuntos
Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/terapia , Humanos , Masculino
16.
Folia Med Cracov ; 60(1): 45-54, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32658211

RESUMO

Takotsubo cardiomyopathy (TCM) represents an acute systolic left ventricular dysfunction typically triggered by severe psychological or physical stress. Oncological patients due to emotional distress of the diagnosis, proinflammatory and prothrombotic nature of cancer and also physical stress often following complex anticancer therapies are at high-risk of TCM. Moreover, there are also few reports of TCM associated with oncological treatment, mostly chemotherapy. Recent data from large registries indicate a surprisingly high incidence of malignancy in TCM, significant differences in clinical characteristics and unfavorable short- and long-term clinical outcomes in this specific group of patients. Therefore, we present two case reports of TCM that occurred during active anticancer therapy. Both women were admitted with suspicion of acute coronary syndrome. The first patient underwent mastectomy two years before due to hormone receptor-positive breast cancer and on admission she was during adjuvant hormonotherapy with tamoxifen. The admission of the second patient was preceded by fifteen fractions of adjuvant external beam radiotherapy due to intermediate-risk endometrial cancer after radical hysterectomy. Based on coronary angiography type I of acute coronary syndrome was excluded. Both patients negated stressful situations in the period immediately before the symptoms onset. Within hospital course baseline apical ballooning observed in both cases fully recovered and enabled subsequent completion of oncological treatment in accordance with adopted treatment protocols without recurrence of TCM. To our knowledge, presented cases are the first reports showing direct relationship between TCM and adjuvant hormonotherapy with tamoxifen or pelvic radiotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia/efeitos adversos , Radioterapia/efeitos adversos , Cardiomiopatia de Takotsubo/etiologia , Tamoxifeno/efeitos adversos , Idoso , Feminino , Humanos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/fisiopatologia
17.
J Urol ; 204(5): 950-955, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32602770

RESUMO

PURPOSE: Men in whom external beam radiotherapy fails are usually placed on delayed hormone therapy. Some of these men have localized recurrence that might be suitable for further local therapy. We describe patterns of recurrence and suitability for focal ablative therapy in those undergoing transperineal template prostate mapping biopsies. MATERIALS AND METHODS: The study included 145 consecutive patients (December 2007 to May 2014) referred with suspicion of recurrence due to rising prostate specific antigen after external beam radiotherapy or brachytherapy who underwent transperineal template prostate mapping biopsies. Suitability for focal ablative therapy required the cancer to be unifocal or unilateral, or bilateral/multifocal with 1 dominant index lesion and secondary lesions with Gleason score 3+3=6 with no more than 3 mm cancer core involvement. RESULTS: Mean patient age was 70.7 (SD 5.8) years. Median prostate specific antigen at time of transperineal template prostate mapping biopsy was 4.5 ng/ml (IQR 2.5-7.7). Overall 75.9% (110) were suitable for a form of focal salvage treatment, 40.7% (59) were suitable for quadrant ablation, 14.5% (21) hemiablation, 14.5% (21) bilateral focal ablation and 6.2% (9) for index lesion ablation. CONCLUSIONS: Three-quarters of patients who have localized radiorecurrent prostate cancer may be suitable for focal ablative therapy to the prostate based on transperineal template prostate mapping biopsies.


Assuntos
Técnicas de Ablação/métodos , Calicreínas/sangue , Recidiva Local de Neoplasia/terapia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/terapia , Terapia de Salvação/métodos , Técnicas de Ablação/efeitos adversos , Idoso , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Seleção de Pacientes , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Próstata/diagnóstico por imagem , Próstata/patologia , Próstata/efeitos da radiação , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Medição de Risco , Terapia de Salvação/efeitos adversos
18.
Bull Cancer ; 107(9): 912-924, 2020 Sep.
Artigo em Francês | MEDLINE | ID: mdl-32653158

RESUMO

Seminomatous (SGCT) and non-seminomatous (NSGCT) germ cell tumors (GCT) are rare but their incidence are increasing. We will discuss different therapeutic strategies in relapse disease: patients with stage I germ cell tumor have an excellent prognosis with a cure rate approaching 98-99 %, whatever the histology and the chosen treatment (surveillance strategy or adjuvant treatment). Relapses are observed among 20% of patients with stage I SGCT or low risk NSGCT and 50 % of patients with high risk NSGCT. Patients are treated according to the international prognosis group (IGCCCG) for SGCT and low risk NSGCT, naïve of chemotherapy. After an adjuvant treatment, the protocol must be adapted to the number of previous cycles (1 or 2 BEP) and to the prognosis group. Five to 50% of patients relapse after a first line of metastatic chemotherapy according to initial prognosis group. Dose-dense chemotherapy according to the GETUG13 protocol reduces the risk of relapse for the patients with poor-risk group NSGCT and unfavorable tumor marker decline. The prognosis of patients with relapsed or refractory GCT after a first line is more negative since only half of them will be cured by salvage standard chemotherapy. An international therapeutic trial (TIGER) is ongoing in first line salvage treatment evaluating high-dose chemotherapy (HDCT) with hematopoietic stem cell transplantation (HSCT). Finally, developing biomarkers for predicting clinical relapse, the management in expert centers of these patients and participation in therapeutic innovation are important perspectives for a better understanding and treatment of these patients with a poorer prognosis.


Assuntos
Recidiva Local de Neoplasia/terapia , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/terapia , Algoritmos , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia
19.
J Cancer Res Ther ; 16(3): 672-674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719289

RESUMO

Metastases to the parotid gland are very rare. We report the second case of bilateral metastases to the parotid gland from a breast invasive ductal carcinoma. A 50-year-old female was treated for an early left breast cancer in 2007. A pulmonary metastatic relapse was diagnosed in 2013. A metastatic skin extension required several lines of treatment from June 2014 to July 2016. Bilateral parotid gland metastases from a breast invasive ductal carcinoma were confirmed in December 2016. The patient died on May 2017 from cerebral metastases. Only 16 cases of metastasis to the parotid gland from breast cancer have been reported in the literature. Only one case had a bilateral involvement. Prognosis is poor, and there are no specific guidelines for the treatment.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Parotídeas/secundário , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Terapia Combinada , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Cuidados Paliativos , Neoplasias Parotídeas/terapia
20.
Expert Opin Pharmacother ; 21(12): 1479-1492, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32486865

RESUMO

INTRODUCTION: Despite, the strong rationale and evidence of the benefit of postoperative intraperitoneal chemotherapy in advanced ovarian cancer, it has not been widely adopted, mainly due to its high morbidity and logistical difficulties. Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a more tolerable and technically feasible method of intraperitoneal chemotherapy, whereas other potential advantages include homogenous drug distribution, application before tumor regrowth and combination with hyperthermia, which is directly cytotoxic and enhances the efficacy of many drugs. AREAS COVERED: In this review, the authors explain the rationale and indications for cytoreductive surgery (CRS) and HIPEC in advanced ovarian cancer. Data of major clinical studies, meta-analyses, and recent randomized trials are discussed. EXPERT OPINION: After many encouraging clinical studies and meta-analyses, a recent randomized study demonstrated survival benefit for HIPEC during interval CRS in primary ovarian cancer, without increased morbidity, whereas another implied its benefit in recurrent ovarian cancer. Results of recently completed and numerous ongoing randomized studies will further determine the benefit of HIPEC in ovarian cancer at different time points. Patient selection and appraisal of the best protocols are crucial. The field of gynecological oncology will most likely evolve to include HIPEC eventually as a routine treatment for ovarian cancer.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/terapia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Terapia Combinada , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto
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