Correlation between treatment-related lymphopenia and pathologic response in esophageal squamous cell carcinoma patients undergoing neoadjuvant chemoradiotherapy / 中华放射肿瘤学杂志

Objective To investigate the relationship between treatment-related lymphopenia and pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC).Methods Clinical data of 220 ESCC patients treated with neoadjuvant CRT followed by surgery between 2002 and 2016 were retrospectively analyzed.Absolute lymphocyte count was determined before and at 1 month after neoadjuvant CRT.Treatment-related lymphopenia was graded using Common Terminology Criteria for Adverse Events (CTCAE,4.0 version).The relationship between lymphopenia,pCR and recurrence was evaluated by chi-square test and Cox's regression model.Results Ninety-five patients (43.2％) achieved a pCR after neoadjuvant CRT and 71 cases (32.3％) recurred postoperatively.During neoadjuvant CRT,the incidence rates of grade 0,1,2,3,and 4 lymphopenia were 1.8％,6.8％,31.4％,38.2％,and 21.8％,respectively.Patients with grade 4 lymphopenia had a significantly lower pCR rate than those with grade 0-3 lymphopenia (22.9％ vs.48.8％,P=0.001).Moreover,grade 4 lymphopenia was significantly associated with a higher risk of recurrence (45.8％ vs.28.5％,P=0.023).Multivariate analysis identified that primary tumor length,tumor location and radiation dose were the independent predictors for grade 4 lymphopenia during neoadjuvant CRT (P=0.013,0.001,0.002).Conclusions The incidence of grade 4 lymphopenia in ESCC patients undergoing neoadjuvant CRT is correlated with a low pCR rate and a high risk of recurrence.Lymphopenia can be used as an economic and effective predictor for pCR.

¿Son el examen clínico, la mamografía y la ecografía métodos confiables para la valoración del tumor residual posterior a neoadyuvancia? / Are the Physical Examination, Ultrasonography and Mammography reliable methods for the assessment of residual tumor following neoadjuvant chemotherapy?

Introducción La quimioterapia neoadyuvante es un tratamiento válido en Estadios II y III de cáncer de mama, con la ventaja de que permite evaluar in vivo la respuesta y realizar mayor número de cirugías conservadoras. Para la decisión terapéutica es muy importante la valoración del tumor residual por clínica y/o por imágenes. Objetivo Determinar la capacidad del examen físico, la mamografía y la ecografía en la valoración del tumor residual y de la respuesta patológica completa. Material y método Examen retrospectivo de 24 pacientes tratadas con neoadyuvancia en el período 2010-2015, evaluadas con los tres métodos diagnósticos previamente al tratamiento quirúrgico. Resultados El tamaño tumoral estimado por cualquiera de los tres métodos tuvo una pobre correlación con el tamaño de la anatomía patológica (Índice kappa < 0,4 para los tres), con una exactitud en ± 0,5 cm del 33,3% para el examen físico, del 22,2% para la mamografía y del 18,2% para la ecografía. La valoración clínica preoperatoria de la axila presentó una sensibilidad del 53,8% y una especificidad del 81,8%. Conclusiones En nuestra experiencia, el examen físico, la mamografía y la ecografía presentan una pobre correlación con el tumor residual, lo que nos lleva a ahondar esfuerzos para mejorar la calidad de los mismos.

Introduction Neoadjuvant chemotherapy is a valid treatment in Stage II and III breast cancer, with the advantage that allows evaluation in vivo response and performs more conservative surgery. For therapeutic decision, it is very important the assessment of residual tumor by clinical examination and/or images. Objective Determine the capacity of physical examination, mammography and ultrasound in the assessment of residual tumor and pathological complete response. Materials and method Retrospective review of 24 patients treated with neoadjuvant chemotherapy between 2010-2015, evaluated with the three diagnostic methods prior to surgical treatment. Results Estimated by any of the three methods, tumor size had a poor correlation with the size of the Pathology (kappa index <0.4 for all three) with an accuracy of ± 0.5 cm 33.3% for physical examination, 22,2% for mammography and 18.2% for ultrasound. Clinical preoperatory assessment of the axilla had a sensitivity of 53.8% and a specificity of 81.8%. Conclusions In our experience, physical examination, mammography and ultrasound have a poor correlation with the residual tumor, leading us to deepen efforts to improve the quality of them.

Consequence of neo-adjuvant chemotherapy on morphology of breast carcinoma: A systematic evaluation.

BACKGROUND: Neo‑adjuvant chemotherapy (NAC) in locally advanced breast cancer is the present trend. Following NAC, a considerable alteration of morphology occurs in the tumor. AIMS: To study effects of NAC on morphology of breast carcinoma and to evaluate the pathologic response (PR). MATERIALS AND METHODS: A total of 39 surgically resected mastectomy specimens of patients of invasive locally advanced breast carcinoma who received NAC were evaluated for macroscopic and microscopic (by routine stains and immunohistochemistry) alteration of morphology. RESULTS: Macroscopically well‑defined tumor noted in 25 cases (64.1%) and in the rest (14 cases, 35.9%), only fibrotic areas identified. Microscopic examination identified malignant cells in 29 (74.4%), significant chronic inflammation in 24 (61.5%), hyalinized fibrosed stroma in 25 (64.1%) and necrosis in 11 (28.2%) cases. Immunohistochemistry assisted in differentiating malignant cells from histiocytes. In 15 cases (38.5%), axillary lymph nodes isolated where fibrosis seen in 12 (30.8%) and malignant cell in 8 (20.5%) cases. In 34 cases where the pre‑treatment biopsy were available, complete pathologic response (pCR) and partial pathologic response (pPR) were achieved in 7 (20.6%) and 23 (67.4%) cases respectively. DISCUSSION: Protocol of systematic evaluation of morphological changes is different in cases of a patient treated by NAC. Nature of malignancy was difficult to categorize as morphology of typical breast carcinomas were altered. Sometimes, immunohistochemistry is advantageous as routine H and E stains are not sufficient to isolate malignant cells in fibrotic and necrotic areas. Appropriate morphological evaluation of the mastectomy specimen is absolutely crucial for assessment of PR and subsequent management.

Pathologic Evaluation of Breast Cancer after Neoadjuvant Therapy

Breast cancer, one of the most common cancers in women, has various treatment modalities. Neoadjuvant therapy (NAT) has been used in many clinical trials because it is easy to evaluate the treatment response to therapeutic agents in a short time period; consequently, NAT is currently a standard treatment modality for large-sized and locally advanced breast cancers, and its use in early-stage breast cancer is becoming more common. Thus, chances to encounter breast tissue from patients treated with NAT is increasing. However, systems for handling and evaluating such specimens have not been established. Several evaluation systems emphasize a multidisciplinary approach to increase the accuracy of breast cancer assessment. Thus, detailed and systematic evaluation of clinical, radiologic, and pathologic findings is important. In this review, we compare the major problems of each evaluation system and discuss important points for handling and evaluating NAT-treated breast specimens.

Treatment Response Evaluation of Breast Cancer after Neoadjuvant Chemotherapy and Usefulness of the Imaging Parameters of MRI and PET/CT

This study was aimed to evaluate the ability of imaging parameters measured on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted MRI (DWI) and positron emission tomography/computed tomography (PET/CT) to serve as response markers in breast cancer after neoadjuvant chemotherapy (NAC). In 20 patients with breast cancer, DCE-MRI and DWI using a 3 T scanner and PET/CT were performed before and after NAC. DCE-MRI was analyzed using an automatic computer-aided detection program (MR-CAD). The response imaging parameters were compared with the pathologic response. The areas under the curve (AUCs) for DCE-MRI using MR-CAD analysis, DWI and PET/CT were 0.77, 0.59 and 0.76, respectively. The combination of all parameters measured by MR-CAD showed the highest diagnostic performance and accuracy (AUC = 0.77, accuracy = 90%). The combined use of the parameters of PET/CT with DCE-MRI or DWI showed a trend toward improved specificity and negative predictive value (100%, 100%, accuracy = 87.5%). The use of DCE-MRI using MR-CAD parameters indicated better diagnostic performance in predicting the final pathological response compared with DWI and PET/CT, although no statistically significant difference was observed. The combined use of PET/CT with DCE-MRI or DWI may improve the specificity for predicting a pathological response.

Histopathologic changes following neoadjuvant chemotherapy in locally advanced breast cancer.

Aims: To compare the clinical and pathologic assessment of response to neoadjuvant chemotherapy and describe the various histopathologic changes observed. Materials and Methods: We studied a group of 40 patients with locally advanced breast cancer who had their initial workup in the form of clinico-imaging assessment of the size and pretreatment biopsy from the lesion. All the patients received two to six cycles of neoadjuvant chemotherapy, either cyclophosphamide 50 to 60 mg/m 2 IV, doxorubicin 40 to 50 mg/m 2 IV and 5-fluorouracil 500 to 800 mg/m 2 IV (CAF) or cyclophosphamide, epirubicin, and 5-fluorouracil (CEF). Clinical and pathologic assessment of response to chemotherapy was done based on the UICC guidelines. Result: Complete clinical response (cCR) was seen in 10% cases (4/40), thirty percent patients had (12/40) partial response and 60% (24/40) had stable disease after neoadjuvant chemotherapy. Pathologic complete response (pCR) with no evidence of viable tumor was observed in 20% patients (8/40). Fifteen patients (37.5%) showed partial response and 42.5% patients (17/40) had a stable disease. No patient progressed during the course of chemotherapy. Changes in the tumor type were observed following chemotherapy, most common being the mucinous change. Histologic changes like dyscohesion, shrinkage of tumor cells, elastosis, collagenization, necrosis, lymphocytic reaction, giant cell response are some of the common observations seen following treatment with neoadjuvant chemotherapy. Conclusion: Pathologic assessment of response to neoadjuvant chemotherapy is a better predictor than the clinical response. The chemotherapy drugs can be modified based on the response observed after 1-2 cycles of neoadjuvant, the response being based on both tumor and patient's responsiveness.

Pathologic and Oncologic Outcomes in Locally Advanced Gastric Cancer with Neoadjuvant Chemotherapy or Chemoradiotherapy

PURPOSE: Although neoadjuvant therapy has been accepted as a treatment option in locally-advanced gastric cancer, its prognostic value has been difficult to evaluate. MATERIALS AND METHODS: Seventy-four gastric cancer patients who underwent gastrectomy after neoadjuvant treatment were divided into two groups according to the pathologic response: favorable (ypT0) and others (ypT1-4). The clinicopathologic characteristics, predictive factors for pathologic response, and oncologic outcome were evaluated. RESULTS: Eleven patients (14.8%) demonstrated ypT0 and the remaining 63 patients (85.2%) were ypT1-4. Chemoradiotherapy (CCRTx) rather than chemotherapy (CTx) was the only predictive factor for a favorable pathologic response. Chemotherapeutic factors and tumor marker levels did not predict pathologic response. The 1-, 2-, and 3-year disease-free survivals were 83.4%, 70%, and 52.2%. The 1-, 3-, 5-year overall survivals were 88.5%, 67.5%, and 51.2%, respectively. Although a complete pathologic response (ypT0N0M0) was achieved in 7 patients, 28.6% of them demonstrated recurrence of the tumor within 6 months after curative surgery. CONCLUSION: CCRTx rather than CTx appears to be more effective for achieving good pathologic response. Although favorable pathologic response has been achieved after neoadjuvant treatment, the survival benefit remains controversial.

Clinical Factors Predicting the Pathologic Tumor Response after Preoperative Concurrent Chemoradiotherapy for Rectal Cancer / 대한방사선종양학회지

PURPOSE: The objective of this retrospective study was to identify predictive factors for the complete pathologic response and tumor downstaging after preoperative concurrent chemoradiotherapy for locally advanced rectal cancer. MATERIALS AND METHODS: Between the years 2000 and 2008, 39 patients with newly diagnosed rectal cancer without prior evidence of distant metastasis received preoperative concurrent chemoradiotherapy followed by surgery. The median radiation dose was 50.4 Gy (range, 45~59.4 Gy). Thirty-eight patients received concurrent infusional 5-fluorouracil and leucovorin, while one patient received oral capecitabine twice daily during radiotherapy. RESULTS: A complete pathologic response (CR) was demonstrated in 12 of 39 patients (31%), while T-downstaging was observed in 24 of 39 patients (63%). N-downstaging was observed in 18 of 28 patients (64%), with a positive node in the CT scan or ultrasound. Two patients with clinical negative nodes were observed in surgical specimens. The results from a univariate analysis indicated that the tumor circumferential extent was less than 50% (p=0.031). Moreover, the length of the tumor was less than 5 cm (p=0.004), while the post-treatment carcinoembryonic antigen (CEA) levels were less than or equal to 3.0 ng/mL (p=0.015) and were significantly associated with high pathologic CR rates. The univariate analysis also indicated that the adenocarcinoma (p=0.045) and radiation dose greater than or equal to 50 Gy (p=0.021) were significantly associated with high T-downstaging, while a radiotherapy duration of less than or equal to 42 days (p=0.018) was significantly associated with N-downstaging. The results from the multivariate analysis indicated that the lesser circumferential extent of the tumor (hazard ratio [HR], 0.150; p=0.028) and shorter tumor length (HR, 0.084; p=0.005) independently predicted a higher pathologic CR. The multivariate analysis also indicated that a higher radiation dose was significantly associated with higher T-downstaging (HR, 0.115; p=0.025), while the shorter duration of radiotherapy was significantly associated with higher N-downstaging (HR, 0.028; p=0.010). CONCLUSION: The circumferential extent of the tumor and its length was a predictor for the pathologic CR, while radiation dose and duration of radiotherapy were predictors for tumor downstaging. Hence, these factors may be used to predict outcomes for patients and to develop further treatment guidelines for high-risk patients.

Phagocytic Function of Retinal Pigment Epithelial Cells toLatex Microspheres in Rabbit :Ultrastructural Findings

Phagocytosis and morphologic changes in the retinal pigment epithelial cell (RPE) were observed after subretinal injection of latex microspheres. Latex microspheres were injected into the subretinal space in the posterior pole of black rabbits through the scleral incision. Five weeks after injection, we enucleated 5 eyeballs which did not show any vitreous or retinal hemorrhage by indirect ophthalmoscopic examination. Choroid and retina of injec-tion site was excised and processed to observe under the transmission electron microscope. The RPE contained numerous latex phagosomes, phagolysosomes, and phagomelanosomes in their cytoplasms. RPE hyperplasia and subretinal membrane were found. These findings suggest that the pathologic response of the RPE, such as proliferation, occur when retinal pigment epithelial cells phagocytize indigestible materials or their intracellular accumulation of phagosome become excessive.