Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment / 北京大学学报(医学版)

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.

Stereotactic radiation therapy in the era of precision medicine for cancer / 中国应用生理学杂志

Unlike conventional radiation therapy, stereotactic radiation therapy (SRT) is an emerging tumor-ablative radiation technology with a high-dose delivery to targets while dramatically sparing adjacent normal tissues. The strengths of SRT involve noninvasive and short-course treatment, high rates of tumor local control with a low risk of side effects. Although the scientific concepts of radiobiology fail to be totally understood currently, SRT has shown its potential and advantages against various tumors, especially for those adjacent to less tolerable normal organs (spinal cord, optic nerve, bowels, etc.). Nowadays, the clinical efficacy of SRT has been widely confirmed in certain patients, especially for those medically inoperable, unwilling to undergo surgery, medicine ineffective with tumor progression. Moreover, SRT could be properly used as palliative treatment aiming at relieving local symptoms and pain, and eventually achieving a potential survival benefit of several months. However, the weaknesses of SRT relate to inevitable radiation-induced toxicities as well as the inaccessibility of prophylactic irradiation. In general, one flaw cannot obscure the splendor of the jade. The emergence and development of SRT has opened the new era of precision radiation therapy, and SRT will probably step gloriously onto the remarkable stage for precision medicine.

Analysis of the factors affecting pathologic complete response to neoadjuvant chemotherapy in breast cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the factors affecting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients.</p><p><b>METHODS</b>A retrospective cohort study was carried out to analyze the clinical data of 141 breast cancer patients treated with neoadjuvant chemotherapy. The factors affecting pCR and the changes of tumor receptor status before and after treatment were analyzed.</p><p><b>RESULTS</b>Among all the 141 patients, 21 patients (14.9%) achieved pCR. The rate of pCR achieved by regimens of anthracycline combined with taxane was higher (16.8%, 19/113) than that by anthracycline-containing regimens (7.1%, 1/14). The dose intensity of anthracycline had a significant correlation with pCR rate (P < 0.05). The pCR rate in the relative dose intensity of taxane ≥ 0.85 arm was higher than that of < 0.85 arm (P = 0.02). Eighty patients (56.7%) had completed more than 4 cycles of chemotherapy and the median time to achieve pCR was 6 (3 to 10) cycles. The pCR rate had a significant difference between patients < 6 and ≥ 6 cycles (7.1% vs. 22.5%,P = 0.01). Multivariate analysis showed that tumor size measured by palpation ≤ 5 cm and ≥ 6 chemotherapy cycles were significantly related with pCR rate (P < 0.05). In all the 21 pCR patients, the pre-treatment ER(-), PR(-), HER-2(-) statuses were in 14, 14 and 17 patients, respectively. The status of ER, PR, HER-2 of most patients (74.2%, 69.7% and 87.7%, respectively) was not changed after treatment. Among the patients with changes in receptor status, ER changed from negative to positive was in the majority (37.1%, 13/35 vs. 12.9%, 4/31, P < 0.05), and the percentage of changes in PR and HER-2 status had no significant differences.</p><p><b>CONCLUSIONS</b>The regimens of anthracycline combined with taxane can achieve a higher pCR rate. The lymph node and receptor status before therapy have no significant correlation with pCR. Patients who have primary tumor size ≤ 5 cm, ≥ 6 chemotherapy cycles and enough dose intensity are easier to achieve pCR. The receptor status before and after therapy should be determined, and according to any positive results, physicians can chose HER-2 targeted therapy and/or endocrine therapy after surgery to benefit the patients.</p>

A clinical study of reasonable doses of docetaxel salvage therapy for patients with metastatic breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the correlation of clinical effects and reasonable doses of docetaxel salvage therapy for patients with metastatic breast cancer.</p><p><b>METHODS</b>We reviewed retrospectively the clinical records of patients with metastatic breast cancer treated with docetaxel and statistically analyzed the correlation between clinical effects and reasonable doses of docetaxel.</p><p><b>RESULTS</b>The objective response rate and clinical benefit rate of docetaxol in patients with metastatic breast cancer were 27.0% and 35.0%, respectively, and the median progression free survival (PFS) was 5.0 (3.8 - 6.3) months. In the analysis at a single dose level, the clinical benefit rate and PFS of the ≥ 90.0 mg/m(2) docetaxel group were superior to that of the < 90.0 mg/m(2) group (P = 0.008, P = 0.045). Multi-dose level group stratified analysis showed that the docetaxel < 75.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) PFS group (P = 0.018), and the ≥ 95.0 mg/m(2) group was better than the 75.0 - 84.9 mg/m(2) group (P = 0.048). In patients who received >third line treatment or previously received paclitaxel adjuvant therapy, the PFS of the ≥ 94.9 mg/m(2) docetaxel group was 6.0 months, better than the 3.0 months of the 75.0 ∼ 84.9 mg/m(2) group (P = 0.031; P = 0.021).</p><p><b>CONCLUSION</b>There is a clear correlation between clinical effects and reasonable doses of docetaxel salvage therapy in patients with metastatic breast cancer.</p>

Efficacy and safety of regimens of capecitabine-based chemotherapy in the treatment of advanced breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate retrospectively the efficacy and toxicity of capecitabine-based chemotherapy in the treatment of advanced breast cancer.</p><p><b>METHODS</b>Three hundred and seventy-six patients with advanced breast cancer were treated with capecitabine-based chemotherapy regimens in our department from Sep 2002 to Sep 2009. They were divided into 3 groups. The group 1 was treated with capecitabine 1000 mg/m(2) orally twice daily on d1-d14, repeated every 3 weeks. The group 2 was treated with capecitabine as group 1, and combined with docetaxel 60 - 75 mg/m(2) intravenous infusion on d1, repeated every 3 weeks. The group 3 was treated with capecitabine as group 1, and combined with vinorelbine 25 mg/m(2) intravenous infusion on d1 and d8, repeated every 3 weeks. The median treatment period of treatment was 3 cycles.</p><p><b>RESULTS</b>Among the 376 patients, 218 patients were evaluable for response. In the group 1 the objective response rate (ORR) was 12.8% and the clinical benefit rate (CBR) was 21.6%. The CBR but not ORR of first line therapy with capecitabine was 35.2%, significantly higher than that of more than first line therapy (17.1%, P < 0.01). The ORRs for group 2 and group 3 were 53.8% and 36.4%, respectively. In the group 2 there was no significant difference in the ORR between the first line therapy and more than first line therapy. In the group 3 the ORR of first line therapy of NX regimen was 36.4%, significantly higher than that of more than first line therapy (16.7%, P < 0.01).</p><p><b>CONCLUSIONS</b>The capecitabine-based chemotherapy is effective and tolerable, and can be used not only in first line but also more than first line therapy. The single agent maintenance chemotherapy after response to combined chemotherapy can prolonge the duration of treatment for patients with metastatic breast cancer.</p>

Comparison of response evaluation methods of neoadjuvant chemotherapy in breast cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the efficiency of response evaluation by clinical examination, ultrasonograghy and mammography in neoadjuvant chemotherapy (NAC) for breast cancer.</p><p><b>METHODS</b>A retrospective cohort study was conducted to analyze the data of 141 patients treated with neoadjuvant chemotherapy. Response evaluation was performed by clinical palpation, ultrasound and mammography.</p><p><b>RESULTS</b>Only 12 (8.5%) among the 141 patients presented with a stage I tumor. The tumor size determined by palpation was often larger than that by ultrasound before therapy (P < 0.01). Among patients with suspicions axillary nodes checked by ultrasound, 88.3% (53/60) of them had positive nodes by pathology before NAC, and 34.5% (10/29) of patients with negative nodes determined by ultrasound had positive nodes by pathology. In all the 141 patients, 21(14.9%) showed pathological complete remission in both the primary tumor and lymph node. For response evaluation, the false complete remission rate judged by clinical examination was 46.8% (22/47), and the false tumor residual rate by ultrasound was 84.0% (21/25). In 53.5% (23/43) of patients the response could not be assessed by mammography due to that the tumors were undistinguishable in size. The range of microcalcification was not reduced in 5 patients with a partial response of the tumor. 25 patients experienced needle puncture during therapy. Among them, in the 9 pathologically negative patients, only 3 achieved pCR, and the other 16 positive patients didn't achieve pCR.</p><p><b>CONCLUSION</b>Using the puncture or sentinel lymph node biopsy, clinicians should pay enough emphasis on the pathological determination of the node status before chemotherapy. Clinicians will make a quite of false judgment of the tumor by clinical examination, ultrasound or mammography. They may use needle puncture during therapy to evaluate the response of neoadjuvant chemotherapy, and the result should be analyzed synthetically.</p>

Selected CD34+ cell autologous transplantation for advanced malignant tumors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine the clinical results of selected CD34(+) cell autologous transplantation in advanced malignant tumors.</p><p><b>METHODS</b>After pretreatment, fifteen patients aged 12 - 70 (49.5) years with various Stage III or IV malignant tumors were given the sorted CD34(+) cells collected by magnetic-activated cell sorting (Clini MACS, Milteny Biotech, Germany).</p><p><b>RESULTS</b>Peripheral blood progenitor cells (PBPC) from the patients were mobilized by chemotherapy and G-CSF 5 micro g/kg per day. CD34(+) cells gave 2.0 - 5 log depletion after cell sorting, with a median yield of CD34(+) selected cells of 2.4 (0.15 - 12.03) x 10(6)/kg. It gave a median recovery of 64 (52 - 81.4)% and median purity of 98.2 (83.2 - 99.7)%. The median time of neutrophil recovery > 1.0 x 10(9)/L and platelet recovery > 20 x 10(9)/L post-transplantation were 14 (8 - 26) days and 13 (11 - 35) days, respectively. On follow-up of 2 - 33 (11) months, the event-free survival rate was 53.3% (8/15) and the overall survival rate was 66.7% (10/15).</p><p><b>CONCLUSION</b>Transplantation of autologous selected PBPC CD34(+) cells gives prompt and stable engraftment. Selected CD34(+) cell transplantation, being a safe approach, may improve the clinical outcome even in patients with advanced malignant tumors.</p>