Volume 102 ·  Issue 31 ·  2022

Bone and soft tissue sarcomas are rare malignancies that present challenges in diagnosis and treatment. With the development of molecular technology, especially the popularization of next-generation sequencing (NGS) technology in the field of tumor, the diagnosis of some bone and soft tissue sarcomas have changed due to new evidence, and the treatment strategy has been adjusted accordingly. Molecular technology is expected to be an important tool of diagnosis and treatment strategy in the future. However, it has not been widely used in the fields of sarcoma, there are still many problems. Based on the data of literatures, the basic research, diagnosis, treatment, prognosis and existing problems of molecular analysis in sarcoma are discussed in this article.

Chemotherapy is the main systemic treatment for patients with advanced soft tissue sarcoma, and immunotherapy is only effective for some special subtypes. Anti-angiogenic small molecule tyrosine kinase inhibitors represented by pazopanib and anlotinib are the main drugs of targeted therapy. They have been clearly recommended as the second-line treatment of non-specific soft tissue sarcoma in guidelines. In recent years, in addition to second-line monotherapy in patients with advanced sarcoma, some studies have been carried out in second-line combination therapy, maintenance therapy, first-line therapy and neoadjuvant therapy. This article briefly reviews the application status and prospect of anti-angiogenic small molecule tyrosine kinase inhibitors in advanced soft tissue sarcoma.

Imaging examination plays an important role in the diagnosis and evaluation of IgG4-related diseases (IgG4-RD), and appropriate examination methods should be selected according to the affected site and clinical diagnosis and treatment needs. According to the evaluation concept of clinical applicability of imaging examination in China, it is necessary for imaging doctors and clinicians to jointly provide reference basis for the reasonable selection of imaging examination methods for patients. This consensus aims at seven common clinical needs of IgG4-RD patients, and briefly outlines the recommendations for the selection of imaging examination methods, aiming at providing the most suitable clinical examination methods, improving the efficiency and effect of diagnosis and treatment, and promoting the rational use of medical resources.

To explore the safety and efficacy of tumor-infiltrating lymphocytes (TILs) extracted from tumor tissue in patients with pulmonary metastasis of osteosarcoma, the TILs were amplified in vitro to reach clinical dosage and reinfused to the patients combined with high-dose interleukin 2 (IL-2).

Twelve subjects with pathologically diagnosed osteosarcoma were enrolled from December 2019 to June 20, 2021 in Shanghai General Hospital. All subjects progressed with metastasis after standard chemotherapy and failed multiple lines of treatments. Fresh tumor tissue was obtained from the metastatic site and extracted and amplified by Good Manufacturing Practice (GMP) workshop to produce TILs to clinical treatment dosage (10⁹-10¹¹). High-dose IL-2 (100 000-200 000 U/kg) was administered immediately after autogenous TILs infusion to promote the activation, proliferation and antitumor cytolytic activity in vivo. Adverse events (AE) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) standard and tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

One patient did not receive treatment due to failure in isolating TILs, total of 11 patients received a single re-infusion of autologous TILs. There were 10 males and 1 female with a median age of 19.9 years (12-33 years). Six of these patients received higher dose levels of 1.0×10¹⁰ TILs. The 11 patients were followed-up for 1 to 13 months and tolerated well. The most common adverse events reported were fever (10/11), constipation (3/11) and elevated gamma-glutamyl transferase (GGT) (3/11). The high incidence of fever was due to the IL-2 infusion. All patients experienced a transient drop in lymphocyte count and leukopenia leading to non-myeloid ablative lymphocyte clearance. The AE included grade 4 hematologic toxicity, including 8 cases of lymphocytopenia, 2 cases of neutropenia and 1 case of thrombocytopenia. No AE of neurotoxicity occurred. Of all the 11 patients, 9 patients got stable disease (SD) and 2 patients had progressive disease (PD). The disease control rate was 9/11. The median duration of SD was more than 4 months, and the maximum tumor volume decreased by close to 20%. Patient number 9 had sustained SD status for more than 6 months.

TILs with in vitro expansion ability could be isolated from tumor tissues of advanced osteosarcoma patients. TILs amplified and reinfused in vitro have anti-osteosarcoma activity.

To investigate the efficacy and safety of the combination therapy with chemotherapy, programmed death-1 (PD-1) inhibitor and anlotinib in the treatment of advanced dedifferentiated liposarcoma (DDLPS).

The clinical data of patients with dedifferentiated liposarcoma who received chemotherapy combined with PD-1 inhibitor and anlotinib in the Department of Medical Oncology, Zhongshan Hospital Affiliated to Fudan University from January 1, 2020 to November 30, 2021 were retrospectively analyzed. A total of 24 patients were included in this study, including 12 males and 12 females, with a median age of onset of 56 years (range, 31-69 years). Efficacy and safety in those patients were assessed.

All patients had unresectable or metastatic dedifferentiated liposarcoma with G2 (moderate differentiation) or G3 (differential differentiation) in a concise three-grade grading scheme of tumor pathology. Twelve patients received the regimen as the first-line treatment, while the other 7 taken the regimen as second-line treatment and 5 as third-line or above. The median follow-up time for overall survival (OS) was 7.7 months. The overall response rate (ORR) was 20.8% (5/24) and disease control rate (DCR) was 83.3% (20/24) with 5 partial response (PR), 15 stable disease (SD) and 4 progressive disease (PD). Overall, the median progression-free survival (PFS) was 4.9 months (95%CI: 3.4-16.2 months). The ORR of anthracycline-based, eribulin-based or gemcitabine-based regimens was 1/12, 2/6 and 2/6, respectively; and the median PFS was 7.7, 7.3 and 4.4 months, respectively. Waterfall plots showed notable tumor shrinkage of any degree in eribulin and gemcitabine-based regimens(3/6 and 2/6, respectively), while there were more patients presented with SD in anthracycline-based group(9/12). Common adverse reactions included myelosuppression, fatigue, anorexia, rash, pruritus, palpitate, hypothyroidism and hypertension.

The combination regimen with chemotherapy, PD-1 inhibitor and anlotinib in the treatment of advanced DDLPS is effective and well tolerable. There are more responders in eribulin or gemcitabine-based regimens.

To explore whether apatinib can reverse the chemotherapy resistance of patients with advanced sarcoma.

The clinical data of advanced sarcoma patients after chemotherapy who received the original chemotherapy regimen combined with low-dose apatinib in Cancer Center of Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from May 2018 to November 2021 were collected retrospectively to evaluate the efficacy and safety of this regimen. The primary end point was progression-free survival (PFS), and the secondary end points were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and adverse events (AE). The patients were grouped according to the diagnosis: osteosarcoma, soft tissue sarcoma and undifferentiated small round cell sarcoma. And the benefits of combination treatment was investigated with the stratified analysis of best outcome of combined therapy, lines of chemotherapy received, best response and PFS of original chemotherapy.

A total of 30 patients were included in this study, including 20 males and 10 females. The mean age was (25.6±14.7) years. There were 9 cases of osteosarcoma, 11 cases of soft tissue sarcoma and 10 cases of undifferentiated small round cell sarcoma. No patient achieved complete response, 8 patients (26.7%) achieved partial response, 19 patients (63.3%) achieved disease stability, the ORR was 26.7%(8/30), and the DCR was 90.0%(27/30). The median PFS and OS were 4.1 and 13.1 months respectively. Among the three different subtypes of sarcoma, the ORR of osteosarcoma was 44.4% (4/9), the median PFS was 4.1 months, and the median OS was not yet achieved; the ORR of undifferentiated small round cell sarcoma was 40% (4/10), the median PFS was 6.4 months, and the median OS was 10.9 months; No response was observed in soft tissue sarcoma, and the median PFS and median OS was 3.5 and 7.3 months respectively. Patients who achieved objective response had better PFS than patients with stable disease (12.8 vs 3.8 months, P=0.015), and patients with PFS≥ 6 months of original chemotherapy had better PFS benefits (12.7 vs 2.7 months, P<0.001). However, the number of original chemotherapy lines and the best response of original chemotherapy had no significant effect on the PFS of this combination regimen. In terms of safety, the related toxicity of apatinib was no more than grade 2, and the grade 4 chemotherapy-related adverse reactions was mainly hematological toxicity, of which 2 patients interrupted treatment because of febrile neutropenia.

Low dose apatinib is effective in reversing chemotherapy resistance of osteosarcoma and undifferentiated small round cell sarcoma with acceptable adverse reactions.

To analyze the clinical phenotype and detect the pathogenic gene in a Chinese pedigree with autosomal dominant polycystic kidney disease(ADPKD).

The proband of this study was hospitalized in Dongguan City People′s Hospital on October 10, 2017, due to "left maxillary apical cyst". Clinical phenotypes were noted, imaging examinations and determination of biochemical indicators were carried out for the clinical diagnosis of the proband. Genomic DNA was extracted from peripheral venous blood. Whole-exome genotyping of the proband was performed with the next generation sequencing technology, and the candidate mutation site of the patient and his family members was verified by PCR and Sanger sequencing technology. The mutation site was further screened in 150 unrelated healthy Chinese controls. Mutation frequency within human populations and bioinformatics analysis were predicted with softwares including ExAC, dbSNP, HGMD, 1000 genomes, ClinVar, PKDB, Mutation Taster and PhyloP.

The proband, a 46-year-old male, was diagnosed with hypertension, positive urine occult blood and elevated blood creatinine. B-ultrasound and CT examinations showed that he had bilateral polycystic kidney with left kidney stones and polycystic liver. The gene analysis showed that the c.11017-10C>A heterozygous splice mutation in PKD1 gene was identified in the proband, his second younger brother, younger sister, daughter and niece, but absent in 150 healthy controls. Bioinformatics analysis showed it has been reported in the dbSNP, ClinVar, HGMD, PKDB and Mutation Taster databases. Some databases predicted it has a harmful function for probably leading to production of a truncated polycystin1(PC1) protein.

c.11017-10C>A underlies the Chinese ADPKD pedigree and expands mutation spectrum of PKD1.

To compare the protective effects of vitamin A eye gel combined with 3M transparent tape and erythromycin eye ointment combined with 3M transparent tape on the eye surface during head and neck surgery under general anesthesia.

From June to December 2021, a total of 120 patients undergoing elective head and neck surgery under general anesthesia in Beijing Tongren Hospital, Capital Medical University were enrolled. Each participant was randomly received vitamin A eye gel (vitamin A eye, n=60) or erythromycin eye ointment (erythromycin eye, n=60), followed by 3M transparent tape on one eye, and taping 3M transparent tape alone for the other eye. The hand-held slit lamp examination was performed 3 times at before induction of anesthesia, after resuscitation in the post anesthesia care unit (PACU) and 1 day after surgery. The primary outcome was corneal fluorescein sodium staining (CFS) score. Secondary outcomes included symptom assessment in dry eye (SANDE) questionnaire score, basic tear secretion test (Schirmer I test, SIt), break-up time (BUT) and incidence of adverse reactions.

Comparison within groups showed that CFS scores were significantly higher in vitamin A eyes and erythromycin eyes at PACU than before induction (P<0.05). Comparison between groups showed that CFS score at PACU in erythromycin eyes (0.62±0.16) was significantly higher than that in vitamin A eyes (0.13±0.01, P=0.007). Compared with before induction, SIt at PACU was significantly increased in the erythromycin eyes [(16.0±1.3) vs (11.4±4.9) mm, P=0.017],and was significantly decreased in vitamin A eyes [(10.2±3.6) vs (12.4±5.5) mm, P=0.046]. The BUT in PACU of erythromycin eyes, vitamin A eyes were (6.4±2.5) s, (6.8±2.1) s, respectively,and were significantly decreased compared with before induction (P<0.05). Comparison between groups showed that there was no significant difference in BUT and SANDE in PACU between two groups (P>0.05). For erythromycin eyes, discomfort symptoms in PACU included viscosity (66.7%, 40/60), conjunctival congestion (21.7%, 13/60), tingling (8.3%, 5/60), blurred vision (58.3%, 35/60). The incidence of these complications in vitamin A eye was 30.0% (18/60), 5.0% (3/60), 0 and 6.7% (4/60), respectively, and all the incidences were significantly higher than those of vitamin A eyes (all P<0.05).

For patients undergoing head and neck surgery under general anesthesia, the combination of vitamin A ocular gel and 3M transparent tape is more effective in prevent postoperative ocular surface injury than the combination of erythromycin ointment and 3M transparent tape.

To investigate the influence of Z-score and different risk factors on positive predictive value (PPV) of noninvasive prenatal testing (NIPT) for chromosome aneuploidies.

A total of 81 838 NIPT samples from January 1, 2016 to May 31, 2021 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Invasive prenatal diagnosis was applied to verify the diagnosis of NIPT-positive results and the corresponding PPV was calculated. The PPV of the samples with different Z-score were compared. The women were divided into high-risk group and non-high-risk group: high-risk group (n=39 114) included those with ultrasound soft index abnormalities, advanced maternal age or high risk for maternal serum screening, while non-high-risk group (n=42 724) included those with intermediate risk for maternal serum screening or no indications. The differences of the PPV between these two groups were compared. Finally, the comprehensive influence of Z-score and different risk factors on PPV were analyzed.

A total of 471 high-risk cases were detected by NIPT results, including 362 cases of trisomy 21, 77 cases of trisomy 18 and 32 cases of trisomy 13. For trisomy 21, trisomy 18 and trisomy 13, there were 226 cases, 46 cases and 6 cases which were confirmed via invasive prenatal diagnosis respectively. The corresponding PPV were 79.3% (226/285), 82.1% (46/56) and 27.3% (6/22), respectively. PPV of trisomy 21 and trisomy 18 were positively correlated with the corresponding Z-score (r=0.92, 0.62, all P<0.05), while trisomy 13 could not be analyzed due to the small sample size. The PPV of high-risk group was 85.2% (207/243), which was higher than that of the non-high-risk group with PPV of 59.2%(71/120, χ²=30.30, P<0.01). When the Z-score was between 3-<4 and 4-<5, the PPV of the high-risk group were 46.2%(12/26)and 62.5%(15/24) respectively, which were higher than those of the non-high-risk group [16.0%(4/25) and 14.3%(3/21), χ²=4.10, 8.90, all P<0.05]. With the increase of Z-score, there was no significant difference in PPV between the two groups (all P>0.05).

The PPV of trisomy 21 and trisomy 18 are positively correlated with Z-score. The PPV of high-risk group is higher than that of non-high-risk group. The combination of Z-score and other risk factors may provide more accurate genetic counseling for those with NIPT positive results.

To compare the safety and efficacy of cryoablation(CYA) and radiofrequency ablation(RFA) for stageⅠnon-small cell lung cancer(NSCLC).

From January 2014 to January 2019, 90 eligible patients [48 males, 42 females, age: 39-85(63.6±10.1)years] in the First Affiliated Hospital of Zhengzhou University met the inclusion criteria were retrospectively analyzed. They were divided into 2 groups according to different treatment methods(group CYA and group RFA). The duration of operation, intraoperative pain, local tumor progression rate and the incidence of complications were compared. The progression-free survival (PFS) and overall survival (OS) of the 2 groups were estimated by Kaplan-Meier curves, and were compared by using log-rank test.

The clinical data and tumor situation of the patients between two groups did not show significant differences. The mean duration of operation for group CYA was longer than that for group RFA [(73.5±17.2)min vs (51.4±18.7)min, P<0.001];the mean intraoperative visual analogue score(VAS)for group CYA was lower than that for group RFA (0.53±0.89 vs 3.44±2.44, P<0.001). The median follow-up period time were 53 months and 52 months for group CYA and RFA. At the end of the study, The local tumor progression rate was 31.6%(12/38) and 25.0%(13/52) for group CYA and group RFA, the difference were not statistically(P=0.491). There was no statistical difference for progress-free survival(PFS)between group CYA and group RFA[51(95%CI:40.3-55.0)months)vs 44(95%CI:37.2-54.1) months, P=0.649]. The median OS was not reached in both groups. The most common complications observed in the two groups were pneumothorax, hemorrhage and pleural effusion. There was no statistical difference in the incidence rates [42.1%(16/38) for group CYA vs 28.8% (15/52)for group RFA, P=0.191]. The incidence rate of pleural effusion for group CYA was higher than that for group RFA [26.3%(10/38)vs 5.8%(3/52), P=0.006]. The incidence rates of pneumothorax and hemorrhage had no statistical difference between the two groups [13.3%(5/38)vs 13.5% (7/52) and 15.8%(6/38) vs 9.6% (5/52), all P>0.05].

Compared with RFA,CYA shows no significant differences in the same efficacy and safety for treating patients with stage Ⅰ NSCLC, with less intraoperative pain but longer operative duration.

To evaluate the related factors of postoperative recurrence intrigeminal neuralgia (TN) patients treated with fully neuroendoscopic microvascular decompression (MVD).

The clinical baseline data and preoperative MRI imaging data of 112 patients with TN treated by neuroendoscopic MVD from December 2008 to December 2020 in the Department of Neurosurgery, Beijing Shijitan Hospital Affiliated to Capital Medical University were retrospectively analyzed, including: area ratio of cerebellopontine area (CPA)(healthy side/affected side), trigeminal nerve(TGN)length ratio(healthy side/affected side), TGN angle ratio(healthy side/affected side), and criminal vessel type. Multivariate Cox proportional hazards model was used to analyze the factors affecting postoperative recurrence.

Among the 112 patients in this group, there were 49 males and 63 females. The age ranged from 20 to 82 (59±9) years, and the course of disease was 0.05 to 30.00 (5.60±5.15) years. Pain was located on the left side in 43 cases (38.39%) and on the right side in 69 cases (61.61%), respectively. All patients were followed up for more than 1 year, with an average follow-up time of 21.5 months, and 11 cases recurred. Multivariate Cox regression analysis revealed that disease duration≥3 years(HR=9.34, 95%CI:1.12-39.07), CPA area ratio(healthy side/affected side)>1 (HR=27.47, 95%CI:1.69-44.20), criminal vessel type with vein(HR=35.39, 95%CI:1.26-18.60) and criminal vessel type with arteriovenous (HR=46.07, 95%CI: 2.74-27.75) were the main factors influencing recurrence of MVD surgery (all P<0.05).

The disease duration≥3 years, CPA area ratio(healthy side/affected side)>1, and criminal vessel type with vein/arteriovenous are the relevant factors that affect the recurrence rate after the fully neuroendoscopic MVD treatment for trigeminal neuralgia.

With the widespread use of high-resolution magnetic resonance vascular wall imaging in the etiological assessment of ischemic stroke, the non-stenotic (luminal stenosis degree<50%) the recognition of high-risk plaques is increasing. Non-stenotic high-risk plaques have certain characteristics in imaging and pathology, and their correlation with stroke occurrence has been confirmed many times in previous studies. At present, the evaluation methods of non-stenotic high-risk plaques mainly include ultrasound, magnetic resonance imaging, CT and PET. However, there is still a lack of uniform standards for the evaluation of non-stenotic high-risk plaques and how to determine whether the detected plaque is the responsible plaque for this stroke, and there is a lack of high-quality evidence-based medical evidence on the best treatment plan for high-risk plaque-related stroke. In the future, the correlation between non-stenotic high-risk plaques and clinical stroke events still needs to be further confirmed by large-sample prospective studies. At the same time, it is necessary to further clarify the dynamic evolution of high-risk plaques with the help of imaging, carry out high-quality randomized controlled studies, further compare the advantages and disadvantages of anticoagulation or antiplatelet therapy and the best opportunity, and find simple evaluation criteria to assist early treatment.

For advanced or unresectable soft tissue sarcomas (STS), traditional treatments do not improve their prognosis very well. With the continuous in-depth research on the immune microenvironment of STS, the application of immunotherapy in STS has received more and more attention, and some patients can be controlled for a long time or even completely relieved after receiving immunotherapy. This article will briefly summarize the research progress of immune checkpoint inhibitors (ICIs), adoptive immunotherapy (ACT) and other immunotherapies (such as oncolytic virus, tumor therapeutic vaccine, etc.) and combination therapy in advanced STS, and make relevant prospects.

Despite the progress in the use of programmed cell death receptor 1 (PD-1) immune checkpoint inhibitors in metastatic lung cancer, most patients still fail to obtain good therapeutic results. Even when combined with first-line double chemotherapy, most patients still showed tumor progression within 12 months. To address this challenge, adoptive cell therapy (ACT) using autologous or allogeneic T cells is a powerful strategy. ACT therapy using tumor infiltrating lymphocytes (TILs) cultured from patient tumors has achieved lasting complete remission in the treatment of metastatic melanoma, and this therapy makes lasting remission of the tumor possible. The durable role of TIL in a variety of epithelial malignancies, including cholangiocarcinoma, cervical cancer, colorectal cancer, and breast cancer, has also been reported. However, this approach has not been evaluated in metastatic lung cancer.

Metastatic breast cancer is an incurable disease for which immune checkpoint inhibitor regimens have limited effects, especially in triple-negative breast cancer. Autologous tumor infiltrating lymphocytes (TILs) is an adoptive cell therapy method that has achieved good therapeutic results in patients with metastatic melanoma. Partial efficacy is currently validated in patients with metastatic epithelioid carcinoma, including breast cancer, by selecting TILs that respond to tumor mutation products.