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PURPOSE: To evaluate the pathological complete response (pCR) rate of locally advanced rectal cancer (LARC) after adaptive high-dose neoadjuvant chemoradiation (CRT) based on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT). METHODS: The primary endpoint was the pCR rate. Secondary endpoints were the predictive value of 18 F-FDG-PET/CT on pathological response and acute and late toxicity. All patients performed 18 F-FDG-PET/CT at baseline (PET0) and after 2 weeks during CRT (PET1). The metabolic PET parameters were calculated both at the PET0 and PET1. The total CRT dose was 45 Gy to the pelvic lymph nodes and 50 Gy to the primary tumor, corresponding mesorectum, and to metastatic lymph nodes. Furthermore, a sequential boost was delivered to a biological target volume defined by PET1 with an additional dose of 5 Gy in 2 fractions. Capecitabine (825 mg/m2 twice daily orally) was prescribed for the entire treatment duration. RESULTS: Eighteen patients (13 males, 5 females; median age 55 years [range, 41-77 years]) were enrolled in the trial. Patients underwent surgical resection at 8-9 weeks after the end of neoadjuvant CRT. No patient showed grade > 1 acute radiation-induced toxicity. Seven patients (38.8%) had TRG = 0 (complete regression), 5 (27.0%) showed TRG = 2, and 6 (33.0%) had TRG = 3. Based on the TRG results, patients were classified in two groups: TRG = 0 (pCR) and TRG = 1, 2, 3 (non pCR). Accepting p < 0.05 as the level of significance, at the Kruskal-Wallis test, the medians of baseline-MTV, interim-SUVmax, interim-SUVmean, interim-MTV, interim-TLG, and the MTV reduction were significantly different between the two groups. 18 F-FDG-PET/CT was able to predict the pCR in 77.8% of cases through compared evaluation of both baseline PET/CT and interim PET/CT. CONCLUSIONS: Our results showed that a dose escalation on a reduced target in the final phase of CRT is well tolerated and able to provide a high pCR rate.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias del Recto , Masculino , Femenino , Humanos , Persona de Mediana Edad , Fluorodesoxiglucosa F18 , Radiofármacos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Quimioradioterapia/efectos adversos , Tomografía de Emisión de Positrones , Terapia Neoadyuvante/efectos adversos , Resultado del TratamientoRESUMEN
In recent years, immune checkpoint inhibitors (ICIs), including nivolumab and pembrolizumab have revolutionized the treatment landscape in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, many patients do not respond to ICIs for reasons that remain largely unknown. For patients who progress on ICIs, chemotherapy and/or biologic therapies are the most widely used treatments based on the clinician's choice, with no defined sequence strategy. We report the experience of a patient with metastatic oropharyngeal squamous cell cancer p16 and human papillomavirus-DNA positive who received chemotherapy with weekly paclitaxel after progressing on nivolumab. Our patient presented a partial response to fourth line paclitaxel, which lasted more than 2 years, with an improvement of his quality of life too. These results support the hypothesis of synergism between immunotherapy and conventional chemotherapies. Even in the setting of immune-refractory disease, immunotherapy may affect tumor immune microenvironment thus leading to a synergistic effect with conventional chemotherapy and achieving unexpected results.
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Neoplasias de Cabeza y Cuello , Nivolumab , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Inmunoterapia/métodos , Recurrencia Local de Neoplasia/terapia , Nivolumab/uso terapéutico , Paclitaxel , Calidad de Vida , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Microambiente TumoralRESUMEN
OBJECTIVES: (1) To investigate whether a contrast-free biparametric MRI (bp-MRI) including T2-weighted images (T2W) and diffusion-weighted images (DWI) can be considered an accurate alternative to the standard multiparametric MRI (mp-MRI), consisting of T2, DWI, and dynamic contrast-enhanced (DCE) imaging for the muscle-invasiveness assessment of bladder cancer (BC), and (2) to evaluate how the diagnostic performance of differently experienced readers is affected according to the type of MRI protocol. METHODS: Thirty-eight patients who underwent a clinically indicated bladder mp-MRI on a 3-T scanner were prospectively enrolled. Trans-urethral resection of bladder was the gold standard. Two sets of images, set 1 (bp-MRI) and set 2 (mp-MRI), were independently reviewed by four readers. Descriptive statistics, including sensitivity and specificity, were calculated for each reader. Receiver operating characteristic (ROC) analysis was performed, and the areas under the curve (AUCs) were calculated for the bp-MRI and the standard mp-MRI. Pairwise comparison of the ROC curves was performed. RESULTS: The AUCs for bp- and mp-MRI were respectively 0.91-0.92 (reader 1), 0.90 (reader 2), 0.95-0.90 (reader 3), and 0.90-0.87 (reader 4). Sensitivity was 100% for both protocols and specificity ranged between 79.31 and 89.66% and between 79.31 and 83.33% for bp-MRI and mp-MRI, respectively. No significant differences were shown between the two MRI protocols (p > 0.05). No significant differences were shown accordingly to the reader's experience (p > 0.05). CONCLUSIONS: A bp-MRI protocol consisting of T2W and DWI has comparable diagnostic accuracy to the standard mp-MRI protocol for the detection of muscle-invasive bladder cancer. The experience of the reader does not significantly affect the diagnostic performance using VI-RADS. KEY POINTS: ⢠The contrast-free MRI protocol shows a comparable accuracy to the standard multiparametric MRI protocol in the bladder cancer muscle-invasiveness assessment. ⢠VI-RADS classification helps non-expert radiologists to assess the muscle-invasiveness of bladder cancer. ⢠DCE should be carefully interpreted by less experienced readers due to inflammatory changes representing a potential pitfall.
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Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Neoplasias de la Vejiga Urinaria , Medios de Contraste , Imagen de Difusión por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética , Masculino , Músculos , Estudios Prospectivos , Estudios Retrospectivos , Sensibilidad y Especificidad , Neoplasias de la Vejiga Urinaria/diagnóstico por imagenRESUMEN
The Liver Imaging Reporting and Data System (LI-RADS) is a recently developed classification aiming to improve the standardization of liver imaging assessment in patients at risk of developing hepatocellular carcinoma (HCC). The LI-RADS v2017 implemented new algorithms for ultrasound (US) screening and surveillance, contrast-enhanced US diagnosis and computed tomography/magnetic resonance imaging treatment response assessment. A minor update of LI-RADS was released in 2018 to comply with the American Association for the Study of the Liver Diseases guidance recommendations. The scope of this review is to provide a practical overview of LI-RADS v2018 focused both on the multimodality HCC diagnosis and treatment response assessment.
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Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Diagnóstico por Imagen/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Imagen Multimodal/métodos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Sistemas de Información Radiológica/estadística & datos numéricos , Resultado del TratamientoRESUMEN
BACKGROUND: Low anterior resection syndrome is significantly associated with a deterioration in the quality of life, and its medical treatment is usually ineffective. OBJECTIVE: The aim of the present study was to establish the efficacy of percutaneous tibial nerve stimulation in treating this syndrome. DESIGN: This is a randomized pilot trial with 1-year follow-up. SETTINGS: The study was conducted in a specialized colorectal unit of a tertiary hospital. PATIENTS: Patients who underwent neoadjuvant chemoradiotherapy and low anterior rectal resection for cancer with low anterior resection syndrome score ≥21 and ileostomy closed at least 18 months earlier were included. INTERVENTIONS: Patients were randomly assigned to receive either percutaneous tibial nerve stimulation plus medical treatment (arm A, n = 6) or medical treatment (arm B, n = 6). Low anterior resection syndrome was assessed using symptom severity and disease-specific quality-of-life scores at baseline, at the end of treatment, and at 1-year follow-up. MAIN OUTCOME MEASURES: The primary outcome was a clinical response, defined as a reduction of the low anterior resection syndrome score. RESULTS: Only in group A low anterior resection syndrome score, fecal incontinence severity index, and obstructed defecation syndrome score improved significantly with treatment (35.8 ± 2.5 vs 29.0 ± 3.8 (p = 0.03); 36.8 ± 4.3 vs 18.5 ± 8.0 (p = 0.02); 10.3 ± 3.9 vs 8.0 ± 4.9 (p = 0.009)) and changes were observed in all domains of quality-of-life instruments. In both groups the symptom severity and quality-of-life scores at 1-year follow-up did not differ significantly from those recorded at the end of treatment. LIMITATIONS: The study had a small number of patients and it was underpowered to detect the within-group effect. CONCLUSIONS: Percutaneous tibial nerve stimulation could be an effective treatment for low anterior resection syndrome. Additional studies are warranted to investigate clinical effectiveness in low anterior resection syndrome. See Video Abstract at http://links.lww.com/DCR/B371. ESTUDIO PILOTO ALEATORIO DE ESTIMULACIÓN PERCUTÁNEA DEL NERVIO TIBIAL POSTERIOR VERSUS TERAPIA MÉDICA PARA EL TRATAMIENTO DEL SÍNDROME DE RESECCIÓN ANTERIOR BAJA: UN AÑO DE SEGUIMIENTO: El síndrome de resección anterior baja se asocia con un deterioro significativo en la calidad de vida y su tratamiento médico generalmente es ineficaz.El objetivo del presente estudio fue establecer la eficacia de la estimulación percutánea del nervio tibial en el tratamiento de este síndrome.Este es un estudio piloto aleatorio con 1 año de seguimiento.El estudio se realizó en una unidad colorrectal especializada de un hospital terciario.Se incluyeron pacientes que se sometieron a quimiorradioterapia neoadyuvante y resección rectal anterior baja por cáncer con puntaje de síndrome de resección anterior baja ≥ 21 e ileostomía cerrada al menos 18 meses antes.Los pacientes fueron asignados aleatoriamente para recibir estimulación percutánea del nervio tibial + tratamiento médico (brazo A, n = 6) o tratamiento médico (brazo B, n = 6). El síndrome de resección anterior baja se evaluó utilizando puntajes de la gravedad de los síntomas y de calidad de vida específicos de la enfermedad al inicio, al final del tratamiento y al año de seguimiento.El resultado primario fue una respuesta clínica, definida como una reducción de la puntuación del síndrome de resección anterior baja.Solo en el grupo A, el puntaje del síndrome de resección anterior baja, el índice de severidad de incontinencia fecal y el puntaje del síndrome de defecación obstruida mejoraron significativamente con el tratamiento (35.8 ± 2.5 vs 29 ± 3.8, p = 0.03; 36.8 ± 4.3 vs 18.5 ± 8.0, p = 0.02; 10.3 ± 3.9 vs 8.0 ± 4.9, p = 0.009, respectivamente) y se observaron cambios en todos los dominios de los instrumentos de calidad de vida. En ambos grupos, los puntajes de severidad de los síntomas y de calidad de vida al año de seguimiento no difirieron significativamente de los registrados al final del tratamiento.El estudio tuvo un pequeño número de pacientes y no logró suficiente poder para detectar el efecto dentro de grupo.La estimulación percutánea del nervio tibial podría ser un tratamiento efectivo para el síndrome de resección anterior baja. Se requieren estudios adicionales para investigar la efectividad clínica en el síndrome de resección anterior baja. Consulte Video Resumen http://links.lww.com/DCR/B371.
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Anastomosis Quirúrgica/efectos adversos , Proctectomía/efectos adversos , Neoplasias del Recto/cirugía , Estimulación Eléctrica Transcutánea del Nervio/métodos , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estreñimiento/epidemiología , Incontinencia Fecal/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/psicología , Complicaciones Posoperatorias/terapia , Calidad de Vida , Índice de Severidad de la Enfermedad , Síndrome , Nervio Tibial/fisiología , Estimulación Eléctrica Transcutánea del Nervio/efectos adversos , Resultado del TratamientoRESUMEN
AIMS AND OBJECTIVES: To assess the effectiveness of a specific home care nursing programme in addition to standard care in patients (pts) receiving oral anticancer treatments. BACKGROUND: Oral anticancer therapy present challenges for pts since treatment is a home-based therapy. This study evaluates the potentiality of a home care nursing programme in decreasing hospital accesses for not severe toxicity. METHODS: This is an open-label, multicentre, randomised trial including pts who were receiving an anticancer oral drug. The study complies with the CONSORT checklist published in 2010. Concomitant use of radiation therapy, intravenous or metronomic therapies, or the intake of previous oral drugs was not allowed. Pts were randomly assigned to home care nursing programme (A) or standard care (B). In arm A, dedicated nurses provided information to pts, a daily record on which pts would take note of drugs and dosages and a telephone monitoring during the first two cycles of therapy. The primary outcome was the reduction in improper hospital accesses for grade 1-2 toxicity according to CTCAE v4.0. RESULTS: Out of 432 randomised pts, 378 were analysed (184 pts in arm A and 194 in arm B). Hospital accesses were observed in 41 pts in arm A and in 42 pts in arm B (22.3% vs. 21.6%, respectively). No difference was detected in proportion of improper accesses between arm A and arm B (29.3% vs. 23.8%, respectively). CONCLUSIONS: Our experience failed to support the role of a specific home care nursing programme for pts taking oral chemotherapy. An improved attention to specific educational practice and information offered to pts can explain these results. RELEVANCE TO CLINICAL PRACTICE: Our results underline the role of nurse educational practice and information offered to patients. A careful nurse information of patients about drugs is essential to reduce toxicities avoiding the opportunity of a specific home monitoring.
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Antineoplásicos/administración & dosificación , Servicios de Atención de Salud a Domicilio/organización & administración , Neoplasias , Enfermería Oncológica/organización & administración , Administración Oral , Femenino , Humanos , Italia , Masculino , Oncología Médica/organización & administración , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/enfermería , TerapéuticaRESUMEN
BACKGROUND: Treatment with fluoropyrimidines and concomitant long-course external radiotherapy (RTE) is the standard of care in locally advanced rectal cancer (LARC) preoperative chemoradiation. A randomized phase II study (RaP/STAR-03) was conducted that aimed to evaluate the activity and safety of the monoclonal antibody anti-epidermal growth factor receptor panitumumab as a single agent in combination with radiotherapy in low-risk LARC preoperative treatment. MATERIALS AND METHODS: Patients had adenocarcinoma of the mid-low rectum, cT3N- or cT2-T3N+, KRAS wild-type status, and negative circumferential radial margin. Panitumumab was administered concomitant to RTE. Rectal surgery was performed 6-8 weeks after the end of preoperative treatment. The adjuvant chemotherapy regimen was FOLFOX. The primary endpoint was the pathologic complete response (pCR) rate. The sample size was calculated using Simon's two-stage design. A pCR of 16% was considered to qualify the experimental treatment for further testing. RESULTS: Ninety-eight patients were enrolled in 13 Italian centers from October 2012 to October 2015. Three panitumumab infusions were administered in 92 (93.4%) patients. The RTE compliance was median dose 50.4 Gy; ≥28 fractions in 82 (83.7%) patients. Surgical treatment was performed in 92 (93.9%) patients, and no severe intraoperative complications were observed. A pCR was observed in 10 (10.9%) patients (95% confidence interval, 4.72%-17.07%). Pathological downstaging occurred in 45 (45.9%) patients. Grade 3 toxicities were observed in 22 (22.3%) patients, and the common adverse events were skin rash in 16 (16.3%) patients. No grade 4 toxicities were reported. CONCLUSION: The pCR rate (our primary endpoint), at only 10.9%, did not reach the specified level considered suitable for further testing. However, the analysis showed a good toxicity profile and compliance to concomitant administration of panitumumab and RTE in preoperative treatment of LARC. The pCR evaluation in all wild-type RAS is ongoing. IMPLICATIONS FOR PRACTICE: The aim of the RaP/STAR-03 study was to evaluate the activity and safety of monoclonal antibody anti-epidermal growth factor receptor (EGFR) panitumumab as a single agent without chemotherapy in low-risk, locally advanced rectal cancer (LARC) preoperative treatment. Nevertheless, the use of panitumumab in combination with radiotherapy in preoperative treatment in patients with KRAS wild type and low-risk LARC did not reach the pathologic complete response primary endpoint. This study showed a good toxicity profile and compliance to combination treatment. Further analysis of NRAS and BRAF on tissue and circulating levels of the EGFR ligands and vascular factors (soluble vascular endothelial growth factor, E-selectin) may provide insight on the potential molecular pathways involved in the anti-EGFR response.
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Antineoplásicos Inmunológicos/uso terapéutico , Quimioradioterapia/métodos , Panitumumab/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Panitumumab/farmacología , Cuidados PreoperatoriosRESUMEN
BACKGROUND: Twenty percent of rectal cancer patients have synchronous distant metastasis at diagnosis. At present, the treatment strategy in this patient setting is not well defined. This study in one institution evaluates the treatment strategy of three different patient groups. PATIENTS AND METHODS: Between January 2000 and July 2011, 65 patients with M1 rectal cancer were evaluated. Three different groups were defined: rectal cancer with resectable metastatic disease (group A); rectal cancer with potentially resectable metastatic disease (group B), and rectal cancer with unresectable metastatic disease (group C). RESULTS: Group A included 11 patients (16.9%), group B 28 patients (43.1%) and group C 26 patients (40%). Forty-three (66.2%) patients underwent surgery for primary rectal cancer, and 30 (46.2%) patients for metastasis resection (23 liver, 4 lung and 3 ovary). Median overall survival (OS) by group was: 51 (5-86; group A), 32 (24-40; group B) and 16 (7-26; group C) months. Patients undergoing metastasis resection have higher median OS than unresected patients (44 vs. 15 months; p < 0.001). CONCLUSIONS: The treatment strategy in synchronous metastatic rectal cancer must consider the possibility of distant metastasis resection. Long-term survival can be achieved using an integrated approach.
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Quimioradioterapia Adyuvante , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Neoplasias Ováricas/terapia , Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Comunicación Interdisciplinaria , Italia , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/secundario , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Preoperative chemotherapy improves the outcome in patients with colorectal cancer with liver metastases. In the current study, the authors evaluated the activity of a conversion treatment with the combination of capecitabine plus oxaliplatin (XELOX) used in association with panitumumab in patients with unresectable, liver-only, metastatic colon cancer. METHODS: Chemotherapy-naive patients with unresectable liver metastases from colon cancer with no other metastatic disease sites were enrolled. All patients received upfront therapy with XELOX plus panitumumab (P-XELOX) and were reevaluated for resectability every 4 cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints were overall survival (OS), progression-free survival, the percentage of patients whose disease became radically resectable, and the safety of the P-XELOX combination. RESULTS: A total of 49 patients were recruited, 35 of whom had wild-type KRAS (wtKRAS) and 14 of whom (who were enrolled before study amendment) had unknown (9 patients) or mutated (5 patients) KRAS mutational status. Forty-six patients were evaluable for response. After conversion P-XELOX therapy, the ORR in the general population was 54%, with 2 complete responses, 23 partial responses, and 14 cases of stable disease. In patients with wtKRAS, the ORR of the patients reached 65% (2 CRs and 19 PRs), which allowed 15 patients with initial unresectable liver metastasis to be reclassified as having resectable disease. Survival analysis demonstrated a median progression-free survival of 8.5 months and a median OS of 21.9 months. Patients who underwent surgery were found to have a significantly better OS when compared with those who did not undergo surgery (P < .001). Overall, toxicities were found to be predictable and manageable, with the most common being cutaneous, gastrointestinal, and neurologic toxicities. CONCLUSIONS: Conversion P-XELOX therapy yields high response and resectability rates for patients with metastatic colon cancer with extensive liver involvement.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Quimioterapia Combinada , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Panitumumab , Resultado del TratamientoRESUMEN
Analysis of plasma-derived cell-free DNA (cfDNA) might allow for the early identification of resistance in metastatic colorectal carcinoma (mCRC) patients receiving anti-EGFR monoclonal antibodies. We tested plasma samples from the Erbitux Metastatic Colorectal Cancer Strategy (ERMES) phase III trial of FOLFIRI+Cetuximab in first-line treatment of RAS/BRAF wild-type mCRC. Samples were collected at baseline (n = 37), at 8 weeks of treatment (n = 32), progressive disease (PD; n = 36) and 3 months after PD (n = 21). cfDNA testing was performed using the Idylla™ ctKRAS and ctNRAS-BRAF tests and the Oncomine Pan-Cancer Cell-Free Assay. Analysis of basal samples revealed RAS/BRAF mutations in 6/37 cases. A transient RAS positivity not associated with PD was observed at 8 weeks in five cases that showed no mutations at baseline and PD. The frequency of mutant cases increased at PD (33.3%) and decreased again at 3 months after PD (9.5%). The median progression-free survival (mPFS) of patients RAS/BRAF mutant at PD was 7.13 months versus 7.71 months in wild-type patients (p = 0.3892). These data confirm that the occurrence of RAS/BRAF mutations in mCRC patients receiving anti-EGFR agents is relatively frequent. However, the cfDNA dynamics of RAS mutations in patients treated with anti-EGFR agents plus polychemotherapy are complex and might not be directly associated with resistance to treatment.
RESUMEN
BACKGROUND: Rectal cancer is a malignant neoplasm of the large intestine resulting from the uncontrolled proliferation of the rectal tract. Predicting the pathologic response of neoadjuvant chemoradiotherapy at an MRI primary staging scan in patients affected by locally advanced rectal cancer (LARC) could lead to significant improvement in the survival and quality of life of the patients. In this study, the possibility of automatizing this estimation from a primary staging MRI scan, using a fully automated artificial intelligence-based model for the segmentation and consequent characterization of the tumor areas using radiomic features was evaluated. The TRG score was used to evaluate the clinical outcome. METHODS: Forty-three patients under treatment in the IRCCS Sant'Orsola-Malpighi Polyclinic were retrospectively selected for the study; a U-Net model was trained for the automated segmentation of the tumor areas; the radiomic features were collected and used to predict the tumor regression grade (TRG) score. RESULTS: The segmentation of tumor areas outperformed the state-of-the-art results in terms of the Dice score coefficient or was comparable to them but with the advantage of considering mucinous cases. Analysis of the radiomic features extracted from the lesion areas allowed us to predict the TRG score, with the results agreeing with the state-of-the-art results. CONCLUSIONS: The results obtained regarding TRG prediction using the proposed fully automated pipeline prove its possible usage as a viable decision support system for radiologists in clinical practice.
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Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/radioterapia , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/radioterapia , Adulto , Anciano , Quimioradioterapia/métodos , Femenino , Humanos , Radioterapia de Intensidad Modulada , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Resultado del TratamientoRESUMEN
Human epidermal growth factor receptor 2 (HER2) is overexpressed and/or amplified in approximately 15-20% of gastric adenocarcinoma (GC) patients. In 2010, the landmark ToGA trial established the combination of trastuzumab plus chemotherapy as the first-line standard of care for HER2-positive GC patients with advanced disease. However, subsequent studies on HER2 targeted therapies in this setting failed to meet their primary endpoints, and not all HER2-positive GC patients benefit from targeted approaches. More recently, novel HER2-directed treatments have been investigated, including trastuzumab deruxtecan (T-Dxd); following the results of the DESTINY-Gastric01 study, T-Dxd received its first U.S. Food and Drug Administration (FDA) approval on 15 January 2021 for the treatment of adults with unresectable, locally advanced, or metastatic GC who have received a prior trastuzumab-based regimen. In this review, we discuss the current HER2-targeted treatments for GC in the advanced disease setting, mainly focusing on emerging new treatments and future research directions.
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BACKGROUND: Preoperative chemoradiotherapy has been widely adopted as the standard of care for stage II-III rectal cancers. However, patients with T3N0 lesions had been shown to have a better prognosis than other categories of locally advanced tumor. Thus, neoadjuvant chemoradiation is likely to be overtreatment in this subgroup of patients. Nevertheless, the low accuracy rate of preoperative staging techniques for detection of node-negative tumors does not allow to check this hypothesis. We analyzed a group of patients with cT3N0 low rectal cancer who underwent neoadjuvant chemoradiotherapy with the purpose of evaluating the incidence of metastatic nodes in the resected specimens. METHODS: Between January 2002 and February 2008, 100 patients with low rectal cancer underwent clinical staging by means of endorectal ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging. All patients received preoperative 5-fluorouracil-based chemoradiotherapy and surgical resection with curative aim. RESULTS: Of 100 patients with locally advanced rectal cancer, 32 were clinically staged as T3N0M0. Pathological analysis showed the presence of lymph node metastases in nine patients (28%) (node-positive group). In the remaining 23 cases, clinical N stage was confirmed at pathology (node-negative group). Node-positive and node-negative groups differ only in the number of ypT3 tumors (P < .01). CONCLUSIONS: Our results indicate that immediate surgery for patients with cT3N0 rectal cancer represents an undertreatment risk in at least 28% of cases, making necessary the use of postoperative chemoradiotherapy. Preoperative chemoradiotherapy should be the therapy of choice on the grounds of the principle that overtreatment is less hazardous than undertreatment for cT3N0 rectal cancers.
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Adenocarcinoma/patología , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Cuidados Preoperatorios , Pronóstico , Dosificación Radioterapéutica , Tasa de SupervivenciaRESUMEN
Synchronous or metachronous liver metastases occur in up to one-third of patients with colorectal cancer and are associated with a poor prognosis. Many evidences have shown that surgical resection can be curative, with 5-year survival rates ranging from 37% to 50%, but many patients are ineligible for surgery because of multiple liver lesions, bilobar distribution of liver metastases, or the presence of widespread extrahepatic disease. The management of unresectable liver metastases includes many therapeutic options such as systemic chemotherapy, selective internal radiation therapy (SIRT) with yttrium-90 (Y-90), targeted therapy, and surgery. These treatments can be integrated into a sequential multimodal approach to increase the resection rate. We present a case in which such an approach was put into practice. The favorable result suggests that SIRT, along with systemic chemotherapy and surgery, is a valid treatment option for unresectable colorectal liver metastases.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Braquiterapia , Neoplasias Colorrectales/patología , Hepatectomía , Neoplasias Hepáticas/terapia , Terapia Recuperativa , Radioisótopos de Itrio/uso terapéutico , Anciano , Anticuerpos Monoclonales Humanizados , Braquiterapia/métodos , Cetuximab , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Terapia Recuperativa/métodosRESUMEN
Colorectal cancer is one of the most commonly diagnosed tumors worldwide and a leading cause of cancer-related death. Although the majority of gastrointestinal cancers are generally considered poorly immunogenic, recent data from clinical trials have demonstrated that the subgroup of patients with DNA mismatch repair system is highly responsive to immune checkpoint inhibitor-based therapy. We present the case of a 74-year-old man with pulmonary autoimmune intersitiopathy and microsatellite instability metastatic colorectal cancer who responded to nivolumab despite the concomitant steroid therapy. Furthermore, his autoimmune disease did not worsen during immunotherapy.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Inestabilidad de Microsatélites , Esteroides/uso terapéutico , Anciano , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Enfermedades Autoinmunes/diagnóstico , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/diagnóstico , Manejo de la Enfermedad , Humanos , Masculino , Metástasis de la Neoplasia , Estadificación de Neoplasias , Esteroides/administración & dosificación , Resultado del TratamientoRESUMEN
OBJECTIVES: The influence of age (<70â¯years and ≥70â¯years) was retrospectively studied on the quality of life (QoL), incidence of side effects (including skin reactions) and efficacy of chemotherapy plus cetuximab in patients with KRAS wild type (WT) metastatic colorectal cancer (mCRC). METHODS: 225 patients of the Observed study (PS 0-1) were retrieved based on age (< 70 and ≥70â¯years) and evaluated through EORTC QLQ-C30 and DLQI questionnaires. RESULTS: The two patient groups (141â¯<â¯70 and 84â¯≥â¯70â¯years, respectively) were balanced with no differences in any of the clinical and pathological characteristics considered. Both groups underwent similar type of first-line chemotherapy plus cetuximab, treatment duration and compliance. Cetuximab therapy caused similar incidence of side effects and impact on QoL in older and younger patients. No difference was observed in progression free survival (PFS) and in disease control rates between the two patient populations. Median overall survival (OS) was higher in patients <70 (27â¯months, 95% CI: 22.7-31.27) than in patients ≥70 (19â¯months, 95% CI: 14.65-23.35) (pâ¯=â¯0.002), which is likely due to higher proportions of metastatic resection (27.0% vs 8.3%; pâ¯=â¯0.001) and utilization of second-line therapy in younger group (58.9% vs 42.9%; pâ¯=â¯0.028). CONCLUSION: The current data suggest that fit older patients with mCRC can be safely treated with a cetuximab-based therapy, as QoL and safety profile do not seem to be affected by age. In addition, age did not impact the choice of chemotherapy to be associated to cetuximab and treatment compliance.
Asunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cetuximab/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Calidad de Vida , Factores de Edad , Anciano , Antineoplásicos Inmunológicos/administración & dosificación , Cetuximab/administración & dosificación , Neoplasias Colorrectales/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
IMPORTANCE: The combination of a triple-drug chemotherapy regimen with an anti-epidermal growth factor receptor (EGFR) agent as a first-line treatment of metastatic colorectal cancer (mCRC) showed promising activity along with safety concerns in single-arm phase 2 trials. The role of maintenance following chemotherapy and anti-EGFR and the optimal regimen to be adopted are not established. OBJECTIVES: To evaluate the activity and safety of cetuximab plus modified FOLFOXIRI (mFOLFOXIRI) and explore the role of maintenance with cetuximab or bevacizumab in RAS and BRAF wild-type mCRC. DESIGN, SETTING, AND PARTICIPANTS: In a prospective, noncomparative, open-label, multicenter, randomized phase 2 trial, patients aged 18 to 75 years with unresectable, previously untreated RAS and BRAF wild-type (before amendment, KRAS wild-type) mCRC were recruited from 21 oncology units in Italy from October 19, 2011, to March 1, 2015 (followed up through May 31, 2017). In total, 323 patients were screened and 143 were randomized to 2 treatment arms to receive as a first-line induction a regimen of mFOLFOXIRI plus cetuximab followed by cetuximab (arm A) or bevacizumab (arm B) until disease progression. Primary analyses were conducted in a modified intention-to-treat population. INTERVENTIONS: mFOLFOXIRI plus cetuximab repeated every 2 weeks for up to 8 cycles, followed by maintenance with cetuximab or bevacizumab until disease progression. MAIN OUTCOMES AND MEASURES: The primary end point was the 10-month progression-free rate (PFR); secondary end points included progression-free and overall survival, response rate, rate of metastases resection, and adverse events. RESULTS: Of 143 patients randomized, 116 (81.1%) (median [interquartile range (IQR)] age, 59.5 [53-67] years; 34 [29.3%] women) had RAS and BRAF wild-type mCRC. At a median (IQR) follow-up of 44.0 (30.5-52.1) months, 10-month PFRs were 50.8% (90% CI, 39.5%-62.2%) in arm A and 40.4% (90% CI, 29.4%-52.1%) in arm B. The overall response rate was 71.6% (95% CI, 62.4%-79.5%). Main grade 3/4 adverse events were neutropenia (occurring in 36 patients [31%]), diarrhea (in 21 patients [18%]), skin toxic effects (in 18 patients [16%]), asthenia (in 11 patients [9%]), stomatitis (in 7 patients [6%]), and febrile neutropenia (in 3 patients [3%]). CONCLUSIONS AND RELEVANCE: Although neither of the 2 arms met the primary end point, the findings indicate that a 4-month induction regimen of mFOLFOXIRI plus cetuximab is feasible and provides relevant activity results, leading to a high surgical resection rate. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02295930.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/administración & dosificación , Camptotecina/análogos & derivados , Cetuximab , Neoplasias Colorrectales/tratamiento farmacológico , Quimioterapia de Mantención , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Cetuximab/administración & dosificación , Cetuximab/efectos adversos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/métodos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Quimioterapia de Mantención/efectos adversos , Quimioterapia de Mantención/métodos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: The objective of our study was to evaluate the diagnostic impact of slice thickness on the detection of endoleaks at MDCT. SUBJECTS AND METHODS: Fifty patients with abdominal aortic aneurysm treated with endovascular repair who had undergone follow-up MDCT were enrolled in this study. Contrast-enhanced images were obtained with a 4-MDCT scanner (1-mm collimation). Images were reconstructed using a 1-mm (set A), 3-mm (set B), or 5-mm (set C) slice width. Each image set was interpreted by two independent readers for the presence of endoleaks and for image quality on a dedicated workstation. Sensitivity, specificity, and positive predictive values of each reading session were compared. RESULTS: The statistical values obtained with sets A and B were significantly higher (p < 0.001) than those obtained with set C. No statistically significant differences were found between the values obtained with sets A and B. CONCLUSION: For the detection of endoleaks at MDCT, the sensitivity of 1- and 3-mm-thick images was significantly higher than that of 5-mm-thick slices. However, no statistically significant differences were found between the 1- and 3-mm image sets; moreover, the use of thinner reconstruction images (1 mm) has the disadvantage of increasing the number of images that must be interpreted and archived.
Asunto(s)
Angiografía/métodos , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Prótesis Vascular , Imagenología Tridimensional/métodos , Tomografía Computarizada por Rayos X/métodos , Procedimientos Quirúrgicos Vasculares/métodos , Anciano , Anciano de 80 o más Años , Anatomía Transversal/métodos , Análisis de Falla de Equipo/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Falla de Prótesis , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/instrumentaciónRESUMEN
Around 20-30% of patients with hepatic metastasis from colorectal cancer can undergo liver resection, but the increased response rate obtained with the addition of monoclonal antibodies to chemotherapy regimens could result in a higher rate of liver surgery. In this report we describe the case of a patient who underwent a liver resection after neoadjuvant treatment with capecitabine, oxaliplatin and bevacizumab and who achieved a complete pathological response of the liver metastasis. A preoperative CT scan demonstrated a partial response to the treatment while 18FDG-PET scan correctly evaluated the complete pathological response in the liver and detected an active interaortocaval lymph node metastasis. New specific studies are required to evaluate the imaging response in metastatic colorectal cancer patients especially after treatment with new, targeted agents.