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Aging Jun 2024The zinc finger DHHC-type containing 1 (ZDHHC1) gene is implicated in the pathogenesis and progression of various malignant tumors, but its precise involvement in...
The zinc finger DHHC-type containing 1 (ZDHHC1) gene is implicated in the pathogenesis and progression of various malignant tumors, but its precise involvement in uterine corpus endometrial carcinoma (UCEC) remains unknown. Thus, this study investigated ZDHHC1 expression in UCEC using publicly available TCGA and Xena databases and elucidated the functions and mechanisms of the ZDHHC1 gene in UCEC progression using bioinformatics and experiments. The correlation between ZDHHC1 expression and prognosis, clinical features, immune cells, and RNA modifications of UCEC was evaluated using nomograms, correlation, ROC, and survival analyses. The impacts of ZDHHC1 overexpression on UCEC progression and mechanisms were explored with bioinformatics and experiments. Our study revealed that ZDHHC1 expression was significantly downregulated in UCEC and correlated with poor prognosis, cancer diagnosis, clinical stage, age, weight, body mass index, histological subtypes, residual tumor, tumor grade, and tumor invasion. Notably, Cox regression analysis and constructed nomograms showed that downregulated ZDHHC1 expression was a prognostic factor associated with poor prognosis in patients with UCEC. Conversely, above-normal ZDHHC1 expression inhibited the cell growth, cell cycle transition, migration, and invasion of UCEC cells, which may be related to the cell cycle, DNA replication, PI3K-AKT, and other pathways that promote tumor progression. Altered ZDHHC1 expression in UCEC was significantly associated with RNA modifications and the changes in cancer immune cell populations, such as CD56 bright NK cells, eosinophils, Th2 cells, and cell markers. In conclusion, considerably reduced ZDHHC1 expression in UCEC is associated with cancer cell growth, metastasis, poor prognosis, immune infiltration, and RNA modifications, revealing the promising potential of ZDHHC1 as a prognostic marker for UCEC.
Topics: Humans; Female; Endometrial Neoplasms; Prognosis; Cell Proliferation; Middle Aged; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Neoplasm Metastasis
PubMed: 38848146
DOI: 10.18632/aging.205899 -
Medicine Jun 2024Gamma knife stereotactic radiosurgery (GKRS) is a recognized safe and effective treatment for brain metastasis; however, some complications can present significant... (Review)
Review
RATIONALE
Gamma knife stereotactic radiosurgery (GKRS) is a recognized safe and effective treatment for brain metastasis; however, some complications can present significant clinical challenges. This case report highlights a rare occurrence of cerebrospinal fluid (CSF) leakage and pneumocranium following GKRS, emphasizing the need for awareness and prompt management of these complications.
PATIENT CONCERNS
A 35-year-old male with a history of malignant neoplasm of the lip in 2015 and perineural spread of malignancy into the left cavernous sinus was treated with GKRS in 2017. The patient was admitted emergently 39 days after discharge due to persistent headache and dizziness.
DIAGNOSES
Brain computed tomography (CT) revealed diffuse bilateral pneumocranium alongside an observation of CSF leakage.
INTERVENTIONS
A surgical procedure involving a left frontal-temporal craniotomy was performed to excise a residual skull base tumor and repair the dura, guided by a navigator system. The conclusive pathological assessment revealed the presence of squamous cell carcinoma markers.
OUTCOMES
The patient exhibited excellent tolerance to the entire procedure and experienced a prompt and uneventful recovery process. After surgery, the symptoms alleviated and CSF leak stopped. The follow-up image showed the pneumocranium resolved.
LESSONS
Pneumocranium due to early-stage post-GKRS is uncommon. The rapid tumor shrinkage and timing of brain metastasis spreading through the dura can lead to CSF leak and pneumocranium. We reviewed current treatment options and presented a successful craniotomy-based dura repair case.
Topics: Adult; Humans; Male; Brain Neoplasms; Cerebrospinal Fluid Leak; Pneumocephalus; Postoperative Complications; Radiosurgery; Tomography, X-Ray Computed
PubMed: 38847695
DOI: 10.1097/MD.0000000000038464 -
Journal For Immunotherapy of Cancer Jun 2024The bispecific T cell-binding antibody blinatumomab (CD19/CD3) is widely and successfully used for the treatment of children with relapsed or refractory B-cell precursor... (Clinical Trial)
Clinical Trial
Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALL.
The bispecific T cell-binding antibody blinatumomab (CD19/CD3) is widely and successfully used for the treatment of children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here, we report the efficacy of a single course of blinatumomab instead of consolidation chemotherapy to eliminate minimal residual disease (MRD) and maintain stable MRD-negativity in children with primary BCP-ALL.Between February 2020 and November 2022, 177 children with non-high-risk BCP-ALL were enrolled in the ALL-MB 2019 pilot study (NCT04723342). Patients received the usual risk-adapted induction therapy according to the ALL-MB 2015 protocol. Those who achieved a complete remission at the end of induction (EOI) received treatment with blinatumomab immediately after induction at a dose of 5 μg/m/day for 7 days and 21 days at a dose of 15 μg/m/day, followed by 12 months of maintenance therapy. MRD was measured using multicolor flow cytometry (MFC) at the EOI, then immediately after blinatumomab treatment, and then four times during maintenance therapy at 3-month intervals.All 177 patients successfully completed induction therapy and achieved a complete hematological remission. In 174 of these, MFC-MRD was measured at the EOI. 143 patients (82.2%) were MFC-MRD negative and the remaining 31 patients had varying degrees of MFC-MRD positivity.MFC-MRD was assessed in all 176 patients who completed the blinatumomab course. With one exception, all patients achieved MFC-MRD negativity after blinatumomab, regardless of the MFC-MRD score at EOI. One adolescent girl with high MFC-MRD positivity at EOI remained MFC-MRD positive. Of 175 patients who had completed 6 months of maintenance therapy, MFC-MRD data were available for 156 children. Of these, 155 (99.4%) were MFC-MRD negative. Only one boy with t(12;21) (p13;q22)/ became MFC-MRD positive again. The remaining 174 children had completed the entire therapy. MFC-MRD was examined in 154 of them, and 153 were MFC-MRD negative. A girl with hypodiploid BCP-ALL showed a reappearance of MFC-MRD with subsequent relapse.In summary, a single 28-day course of blinatumomab immediately after induction, followed by 12 months of maintenance therapy, is highly effective in achieving MRD-negativity in children with newly diagnosed non-high risk BCP-ALL and maintaining MRD-negative remission at least during the treatment period.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Male; Antibodies, Bispecific; Consolidation Chemotherapy; Maintenance Chemotherapy; Neoplasm, Residual; Pilot Projects; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38844406
DOI: 10.1136/jitc-2023-008213 -
The European Respiratory Journal Jun 2024The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown.
METHODS
EORTC-1205-LCG was a multicentric, noncomparative phase 2 trial, 1:1 randomising between immediate (arm A) and deferred surgery (arm B), followed or preceded by chemotherapy. Eligible patients (Eastern Cooperative Oncology Group 0-1) had treatment-naïve, borderline resectable T1-3 N0-1 M0 mesothelioma of any histology. Primary outcome was rate of success at 20 weeks, a composite end-point including 1) successfully completing both treatments within 20 weeks; 2) being alive with no signs of progressive disease; and 3) no residual grade 3-4 toxicity. Secondary end-points were toxicity, overall survival, progression-free survival and process indicators of surgical quality.
FINDINGS
69 patients were included in this trial. 56 (81%) patients completed three cycles of chemotherapy and 58 (84%) patients underwent surgery. Of the 64 patients in the primary analysis, 21 out of 30 patients in arm A (70.0%; 80% CI 56.8-81.0%) and 17 out of 34 patients (50.0%; 80% CI 37.8-62.2%) in arm B reached the statistical end-point for rate of success. Median progression-free survival and overall survival were 10.8 (95% CI 8.5-17.2) months and 27.1 (95% CI 22.6-64.3) months in arm A, and 8.0 (95% CI 7.2-21.9) months and 33.8 (95% CI 23.8-44.6) months in arm B. Macroscopic complete resection was obtained in 82.8% of patients. 30- and 90-day mortality were both 1.7%. No new safety signals were found, but treatment-related morbidity was high.
INTERPRETATION
EORTC 1205 did not succeed in selecting a preferred sequence of pre- or post-operative chemotherapy. Either procedure is feasible with a low mortality, albeit consistent morbidity. A shared informed decision between surgeon and patient remains essential.
Topics: Humans; Male; Female; Middle Aged; Pleural Neoplasms; Aged; Mesothelioma; Adult; Mesothelioma, Malignant; Neoplasm Staging; Progression-Free Survival; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Combined Modality Therapy; Pleura; Pneumonectomy
PubMed: 38843916
DOI: 10.1183/13993003.02114-2023 -
Journal of Cancer Research and Clinical... Jun 2024The neoadjuvant chemotherapy (NACT) regimen for triple negative breast cancer (TNBC) primarily consists of anthracyclines and taxanes, and the addition of platinum-based... (Comparative Study)
Comparative Study
Comparison of the efficacy of taxanes with carboplatin and anthracyclines with taxanes in neoadjuvant chemotherapy for stage II-III triple negative breast cancer: a retrospective analysis.
PURPOSE
The neoadjuvant chemotherapy (NACT) regimen for triple negative breast cancer (TNBC) primarily consists of anthracyclines and taxanes, and the addition of platinum-based drugs can further enhance the efficacy. However, it is also accompanied by more adverse events, and considering the potential severe and irreversible toxicity of anthracyclines, an increasing number of studies are exploring nonanthracycline regimens that combine taxanes and platinum-based drugs.
METHODS
The retrospective study included 273 stage II-III TNBC patients who received NACT. The AT group, consisting of 195 (71.4%) patients, received a combination of anthracyclines and taxanes, while the TCb group, consisting of 78 (28.6%) patients, received a combination of taxanes and carboplatin. Logistic regression analysis was performed to evaluate the factors influencing pathological complete response (pCR) and residual cancer burden (RCB). The log-rank test was used to assess the differences in event-free survival (EFS) and overall survival (OS) among the different treatment groups. Cox regression analysis was conducted to evaluate the factors influencing EFS and OS.
RESULTS
After NACT and surgery, the TCb group had a higher rate of pCR at 44.9%, as compared to the AT group at 31.3%. The difference between the two groups was 13.6% (OR = 0.559, 95% CI 0.326-0.959, P = 0.035). The TCb group had a 57.7% rate of RCB 0-1, which was higher than the AT group's rate of 42.6%. The difference between the two groups was 15.1% (OR = 0.543, 95% CI 0.319-0.925, P = 0.024), With a median follow-up time of 40 months, the TCb group had better EFS (log-rank, P = 0.014) and OS (log-rank, P = 0.040) as compared to the AT group. Clinical TNM stage and RCB grade were identified as independent factors influencing EFS and OS, while treatment group was identified as an independent factor influencing EFS, with a close-to-significant impact on OS.
CONCLUSION
In stage II-III triple TNBC patients, the NACT regimen combining taxanes and carboplatin yields higher rates of pCR and significant improvements in EFS and OS as compared to the regimen combining anthracyclines and taxanes.
Topics: Humans; Triple Negative Breast Neoplasms; Female; Retrospective Studies; Carboplatin; Anthracyclines; Neoadjuvant Therapy; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Adult; Taxoids; Aged; Neoplasm Staging
PubMed: 38836955
DOI: 10.1007/s00432-024-05738-x -
Cancer Immunology, Immunotherapy : CII Jun 2024To investigate the feasibility and potential clinical value of local consolidative therapy (LCT) in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer...
Oligo-residual disease in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer: incidence, pattern of failure, and clinical value of local consolidative therapy.
OBJECTIVES
To investigate the feasibility and potential clinical value of local consolidative therapy (LCT) in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
PD-1/PD-L1 inhibitor-treated metastatic NSCLC patients with measurable disease in three academic centers were screened and those with adequate follow-up were included. Oligo-residual disease (ORD) was defined as residual tumors limited to three organs and five lesions evaluated at the best response among patients with partial response or stable disease after PD-1/PD-L1 inhibitors. Oligometastatic and multiple-metastatic disease (OMD/MMD) were similarly classified at baseline. Locoregional interventions, administered after effective treatment of PD-1/PD-L1 inhibitors and before initial disease progression, were defined as LCT. Patterns of initial progressive disease (PD) were classified as involving only residual sites (RP), only new sites (NP), or a combination of both (BP).
RESULTS
Among the 698 patients included, ORD was documented in 73 (47.1%) of 155 patients with baseline OMD and 60 (11.0%) of 543 patients with baseline MMD. With a median follow-up of 31.0 (range, 6.0-53.0) months, 108 patients with ORD developed initial PD, with RP, NP, and BP occurring in 51 (47%), 23 (21.3%), and 34 (31.5%), respectively. Among the 133 patients with ORD, those receiving LCT (n = 43) had longer progression-free survival (HR = 0.58, 95% CI 0.40-0.85, p = 0.01) and overall survival (HR = 0.49, 95% CI 0.30-0.79, p < 0.0001).
CONCLUSION
ORD occurs with a clinically relevant frequency among PD-1/PD-L1 inhibitor-treated metastatic NSCLC patients and LCT may provide extra survival benefits in those with ORD.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Male; Lung Neoplasms; Female; Middle Aged; Aged; Immune Checkpoint Inhibitors; Adult; Neoplasm, Residual; B7-H1 Antigen; Aged, 80 and over; Programmed Cell Death 1 Receptor; Incidence; Neoplasm Metastasis; Follow-Up Studies; Retrospective Studies
PubMed: 38833011
DOI: 10.1007/s00262-024-03720-7 -
Cancer Medicine Jun 2024En-Bloc transurethral resection of bladder tumor (ERBT) was clinically used to resect non-muscle-invasive bladder cancer (NMIBC). However, discrepancies persist... (Meta-Analysis)
Meta-Analysis Review Comparative Study
BACKGROUND
En-Bloc transurethral resection of bladder tumor (ERBT) was clinically used to resect non-muscle-invasive bladder cancer (NMIBC). However, discrepancies persist regarding the comparisons between ERBT and conventional transurethral resection of bladder tumor (cTURBT).
METHODS
We conducted a comprehensive search in PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and performed manual searches of reference lists to collect and extract data. Data evaluation was carried out using Review Manager 5.4.0, Rx64 4.1.3, and relevant packages.
RESULTS
There were nine eligible meta-analyses and nine eligible RCTs in our study. NMIBC patients undergoing ERBT were significant associated with a lower rate of bladder perforation and obturator nerve reflex compared to those receiving cTURBT. Our pooled result indicated that ERBT and cTURBT required similar operation time. Regarding postoperative outcomes, ERBT demonstrated superior performance compared to cTURBT in terms of detrusor muscle presence, catheterization time, and residual tumor. ERBT exhibited a higher rate of three-month recurrence-free survival (RFS) compared to those receiving cTURBT (p < 0.05; I = 0%). In bipolar subgroup, ERBT had a significant better 12-month RFS than cTURBT (p < 0.05; I = 0%). Simultaneously, the exclusion of Hybrid Knife data revealed a significant improvement in 12-month RFS associated with ERBT (p < 0.05; I = 50%).
CONCLUSION
Using a combination of umbrella review and meta-analysis, we demonstrated that ERBT had better or comparable perioperative outcome and improved 3 and 12 month RFS than cTURBT. We suggest that ERBT maybe a better surgical method for patients with NMIBC compared with cTURBT.
Topics: Humans; Urinary Bladder Neoplasms; Cystectomy; Treatment Outcome; Urethra; Neoplasm Invasiveness; Non-Muscle Invasive Bladder Neoplasms
PubMed: 38819629
DOI: 10.1002/cam4.7323 -
International Journal of Hyperthermia :... 2024The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation...
PURPOSE
The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation therapy (EBRT) has been proposed as an effective option. This study evaluates outcomes for inoperable residual/recurrent differentiated thyroid cancer (rDTC) patients treated with RFA followed by EBRT.
MATERIALS AND METHODS
Patients with rDTC treated with RFA followed by EBRT were retrospectively studied. RFA was performed using a free-hand, 'moving-shot' technique under US or CT guidance. For lesions invading critical structures intolerant to 'en bloc' high-temperature RFA, limited-field EBRT using 6- or 10-MV photons was used for adjuvant treatment at a dose of 66 Gy in 33 daily fractions. Toxicities and outcomes were reviewed.
RESULTS
Between April 2020 and January 2022, 11 patients with 14 rDTC lesions underwent RFA followed by EBRT. Five patients had metastatic lesions at rDTC diagnosis. With a median follow-up period of 33.7 months, all patients maintained locoregional control, while achieving a 2-year survival rate of 90.9%. This combined treatment achieved a volume reduction ratio of 92.1% ± 5.1%. The mean nadir thyroglobulin level in patients without initial distant metastases after treatment was 1.40 ± 0.81 ng/ml. Regarding treatment-related complications, one patient (9%) experienced temporary hoarseness after RFA, grade 2 radiation dermatitis occurred in 3 patients (27.2%), and grade 2 dysphagia was noted in 4 patients (36.4%). No grade 3 or greater toxicities occurred.
CONCLUSIONS
Salvage RFA followed by EBRT is feasible, effective and safe for patients with rDTC.
Topics: Humans; Thyroid Neoplasms; Male; Female; Middle Aged; Radiofrequency Ablation; Adult; Aged; Salvage Therapy; Retrospective Studies; Neoplasm Recurrence, Local
PubMed: 38816274
DOI: 10.1080/02656736.2024.2358054 -
American Society of Clinical Oncology... Jun 2024The management of axillary lymph nodes in breast cancer is continually evolving. Recent data now support omitting axillary lymph node dissection (ALND) in most patients... (Review)
Review
Personalizing Locoregional Therapy in Patients With Breast Cancer in 2024: Tailoring Axillary Surgery, Escalating Lymphatic Surgery, and Implementing Evidence-Based Hypofractionated Radiotherapy.
The management of axillary lymph nodes in breast cancer is continually evolving. Recent data now support omitting axillary lymph node dissection (ALND) in most patients with metastases in up to two sentinel lymph nodes (SLNs) during upfront surgery and those with residual isolated tumor cells after neoadjuvant chemotherapy (NACT). In the upfront surgery setting, ALND is still indicated, however, in patients with clinically node-positive breast cancer or more than two positive SLNs and, after NACT, in case of residual micrometastases and macrometastases. Omission of the sentinel lymph node biopsy (SLNB) can be considered in many postmenopausal patients with small luminal breast cancer, particularly when axillary ultrasound is negative. Several randomized controlled trials (RCTs) are currently aiming at eliminating the remaining indications for ALND and also establishing omission of SLNB in a broader patient population. The movement to deescalate axillary staging is in part because of the association between ALND and lymphedema, which is swelling of an extremity because of lymphatic damage and obstructed lymphatic drainage. To reduce the risk of developing this condition, patients undergoing ALND can undergo reverse mapping of the axilla and immediate reconstruction or bypass of the lymphatics from the involved extremity. Decongestion and compression are the foundation of conservative treatment for established lymphedema, while lymphovenous bypass and lymph node transfer are surgical procedures to address the physiologic dysfunction. Radiotherapy is an essential component of breast locoregional therapy: more than three decades of radiation research has optimized treatment according to patient's risk of local recurrence while substantially reducing the number of treatment visits. High-quality RCTs have shown the efficacy and safety of hypofractionation-more than 2Gy radiation dose per treatment (fraction)-significantly reducing the burden of radiotherapy treatment for many patients with breast cancer. In 2024, guidelines recommend no more than 15-16 fractions for whole-breast and nodal radiotherapy, with some recommending five fractions for whole-breast radiotherapy. In addition, simultaneous integrated boost (SIB) has been shown to be noninferior to sequential boost with regards to ipsilateral breast tumor recurrence with similar or reduced long-term side effects, also reducing overall treatment length. Further RCTs are underway investigating other indications for five fractions, including SIB and regional node irradiation, such that, in future, it may be possible for the majority of breast radiotherapy patients to be treated with a 1-week course. This manuscript serves to outline the latest updates on axillary surgical staging, lymphatic surgery, and evidence-based radiotherapy in the treatment of breast cancer.
Topics: Humans; Breast Neoplasms; Female; Axilla; Lymph Node Excision; Radiation Dose Hypofractionation; Lymphatic Metastasis; Sentinel Lymph Node Biopsy; Combined Modality Therapy; Lymph Nodes; Neoplasm Staging; Neoadjuvant Therapy
PubMed: 38815195
DOI: 10.1200/EDBK_438776 -
Breast Cancer Research and Treatment Aug 2024Breast cancer remains the most commonly diagnosed cancer in women. Breast-conserving surgery (BCS) is the standard approach for small low-risk tumors. If the efficacy of...
BACKGROUND
Breast cancer remains the most commonly diagnosed cancer in women. Breast-conserving surgery (BCS) is the standard approach for small low-risk tumors. If the efficacy of cryoablation is demonstrated, it could provide a minimally invasive alternative to surgery.
PURPOSE
To determine the success of ultrasound-guided cryoablation in achieving the absence of Residual Invasive Cancer (RIC) for patients with ER + /HER2- tumors ≤ 2cm and sonographically negative axillary nodes.
MATERIALS AND METHODS
This prospective study was carried out from April 2021 to June 2023, and involved 60 preoperative cryoablation procedures on ultrasound-visible, node-negative (cN0) infiltrating ductal carcinomas (IDC). Standard diagnostic imaging included mammography and tomosynthesis, supplemented by ultrasound-guided biopsy. MRI was performed in patients with associated intraductal carcinoma (DCIS) and an invasive component on core needle biopsy (18 out of 22 cases). All tumors were tagged with ferromagnetic seeds. A triple-phase protocol (freezing-thawing-freezing) with Argon was used, with an average procedure duration of 40 min. A logistic regression model was applied to determine significant correlation between RIC and the study variables.
RESULTS
Fifty-nine women (mean age 63 ± 8 years) with sixty low-risk unifocal IDC underwent cryoablation prior to surgery. Pathological examination of lumpectomy specimens post-cryoablation revealed RIC in only one of 38 patients with pure IDC and in 4 of 22 mixed IDC/DCIS cases. All treated tumors had clear surgical margins, with no significant procedural complications.
CONCLUSIONS
Cryoablation was effective in eradicating 97% of pure infiltrating ER + /HER2-tumors ≤ 2cm, demonstrating its potential as a surgical alternative in selected patients.
Topics: Humans; Female; Cryosurgery; Breast Neoplasms; Middle Aged; Aged; Receptor, ErbB-2; Prospective Studies; Prognosis; Neoplasm, Residual; Adult; Receptors, Estrogen; Carcinoma, Ductal, Breast; Mastectomy, Segmental; Aged, 80 and over; Preoperative Care
PubMed: 38814508
DOI: 10.1007/s10549-024-07325-7