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BMC Cancer Nov 2023Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic... (Randomized Controlled Trial)
Randomized Controlled Trial
Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial).
BACKGROUND
Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT).
METHODS
A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness.
DISCUSSION
This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness.
TRIAL REGISTRATION
This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.
Topics: Humans; Neoadjuvant Therapy; Quality of Life; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Rectal Neoplasms; Chemoradiotherapy; Neoplasm Staging
PubMed: 37923987
DOI: 10.1186/s12885-023-11363-7 -
BJS Open May 2024Neoadjuvant therapy has an established role in the treatment of patients with colorectal cancer. However, its role continues to evolve due to both advances in the... (Review)
Review
BACKGROUND
Neoadjuvant therapy has an established role in the treatment of patients with colorectal cancer. However, its role continues to evolve due to both advances in the available treatment modalities, and refinements in the indications for neoadjuvant treatment and subsequent surgery.
METHODS
A narrative review of the most recent relevant literature was conducted.
RESULTS
Short-course radiotherapy and long-course chemoradiotherapy have an established role in improving local but not systemic disease control in patients with rectal cancer. Total neoadjuvant therapy offers advantages over short-course radiotherapy and long-course chemoradiotherapy, not only in terms of increased local response but also in reducing the risk of systemic relapses. Non-operative management is increasingly preferred to surgery in patients with rectal cancer and clinical complete responses but is still associated with some negative impacts on functional outcomes. Neoadjuvant chemotherapy may be of some benefit in patients with locally advanced colon cancer with proficient mismatch repair, although patient selection is a major challenge. Neoadjuvant immunotherapy in patients with deficient mismatch repair cancers in the colon or rectum is altering the treatment paradigm for these patients.
CONCLUSION
Neoadjuvant treatments for patients with colon or rectal cancers continue to evolve, increasing the complexity of decision-making for patients and clinicians alike. This review describes the current guidance and most recent developments.
Topics: Humans; Neoadjuvant Therapy; Colorectal Neoplasms; Immunotherapy; Rectal Neoplasms; Chemoradiotherapy
PubMed: 38747103
DOI: 10.1093/bjsopen/zrae038 -
European Journal of Obstetrics,... Aug 2023This review aims to provide a comprehensive description of surgical approaches for the management of uterine sarcomas. Uterine sarcomas are rare uterine neoplasms.... (Review)
Review
This review aims to provide a comprehensive description of surgical approaches for the management of uterine sarcomas. Uterine sarcomas are rare uterine neoplasms. Frequently, diagnosis is made after hysterectomy or myomectomy scheduled for presumed benign leiomyomas. The gold standard for surgical treatment of uterine sarcomas is hysterectomy with bilateral salpingo-oophorectomy. It is possible to adopt a fertility-sparing approach for those patients who wish to maintain their fertility. The role of pelvic lymphadenectomy is controversial; in fact, removal of lymph nodes is only recommended in the case of radiological suspicion of nodal involvement. Use of a morcellator is associated with increased risk of total recurrence, intra-abdominal recurrence and death. Advanced disease management should be customized based on the patient's performance status given the uncertain role of adjuvant chemotherapy. Treatment of advanced or recurrent disease remains a subject of debate, but surgery is the best approach in terms of morbidity and mortality. There are few options for management of these uterine tumours, and further studies are needed to clarify the diagnostic and therapeutic pathways of patients with a first diagnosis of uterine sarcoma and patients with relapse of uterine sarcoma. No specific evidence supports the adoption of adjuvant therapy in uterine-confined disease, and molecular/genomic profiling may be useful to identify patients at risk of recurrence.
Topics: Female; Humans; Neoplasm Recurrence, Local; Sarcoma; Uterine Neoplasms; Leiomyoma; Pelvic Neoplasms; Hysterectomy
PubMed: 37348383
DOI: 10.1016/j.ejogrb.2023.06.016 -
European Journal of Cancer (Oxford,... Dec 2023The aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1-2 endometrioid ovarian carcinoma apparently... (Observational Study)
Observational Study
OBJECTIVE
The aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1-2 endometrioid ovarian carcinoma apparently confined to the ovary, according to surgical staging.
METHODS
Multicenter, retrospective, observational cohort study. Patients with endometrioid ovarian carcinoma, surgical procedure performed between May 1985 and December 2019, stage pT1 N0/N1/Nx, grade 1-2 were included. Patients were stratified according to lymphadenectomy (defined as removal of any lymph node versus no lymph node assessment), and subgroup analyses according to tumor grade were performed. Kaplan-Meier curves and cox regression analyses were used to perform survival analyses.
RESULTS
298 patients were included. 199 (66.8 %) patients underwent lymph node assessment. Of these, 166 (83.4 %) had unilateral/bilateral pelvic and para-aortic/caval lymphadenectomy. Eleven (5.5 %) patients of those who underwent lymph node assessment showed pathologic metastatic lymph nodes (FIGO stage IIIA1). Twenty-seven patients (9.1 %) had synchronous endometrioid endometrial cancer. After a median follow up of 45 months (95 %CI:37.5-52.5), 5-year DFS and OS of the entire cohort were 89.8 % and 96.2 %, respectively. Age ≤ 51 years (HR=0.24, 95 %CI:0.06-0.91; p = 0.036) and performance of lymphadenectomy (HR=0.25, 95 %CI: 0.07-0.82; p = 0.022) represented independent protective factors toward risk of death. Patients undergoing lymphadenectomy had better 5-year DFS and OS compared to those not receiving lymphadenectomy, 92.0 % versus 85.6 % (p = 0.016) and 97.7 % versus 92.8 % (p = 0.013), respectively. This result was confirmed after exclusion of node-positive patients. When stratifying according to tumor grade (node-positive excluded), patients with grade 2 who underwent lymphadenectomy had better 5-year DFS and OS than those without lymphadenectomy (93.0 % versus 83.1 %, p = 0.040 % and 96.5 % versus 90.6 %, p = 0.037, respectively).
CONCLUSION
Staging lymphadenectomy in grade 2 endometrioid ovarian carcinoma patients was associated with improved DFS and OS. Grade 1 and grade 2 might be considered as two different entities, which could benefit from different approach in terms of surgical staging. Prospective studies, including molecular profiles are needed to confirm the survival drivers in this rare setting.
Topics: Female; Humans; Middle Aged; Retrospective Studies; Prospective Studies; Neoplasm Staging; Lymph Nodes; Carcinoma, Endometrioid; Lymph Node Excision; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Endometrial Neoplasms
PubMed: 37890354
DOI: 10.1016/j.ejca.2023.113398 -
Seminars in Interventional Radiology Aug 2023Uterine fibroids are the most common benign neoplasm of the female pelvis and have a lifetime prevalence exceeding 80% among African American women and approaching 70%... (Review)
Review
Uterine fibroids are the most common benign neoplasm of the female pelvis and have a lifetime prevalence exceeding 80% among African American women and approaching 70% among Caucasian women. Approximately 50% of women with fibroids experience symptoms which can range from heavy menstrual bleeding and bulk-related symptoms such as pelvic pressure with bladder and bowel dysfunction to reproductive dysfunction (e.g., infertility or obstetric complications) and pain. The choice of treatment is primarily guided by the type of symptoms in the individual patient and whether they prefer to retain fertility. While hysterectomy provides definitive resolution of fibroid symptoms and remains the most common treatment option, this procedure is invasive with a long recovery window. Radiofrequency ablation (RFA) is now emerging as a uterine preserving and minimally invasive therapy for symptomatic fibroids. Since its introduction, growing evidence for safety and efficacy of RFA has been generated with low rates of complications. This review will discuss RFA for the management of symptomatic uterine fibroids with a special focus on technical approaches, short- and long-term outcomes including fertility outcomes.
PubMed: 37575346
DOI: 10.1055/s-0043-1770734 -
International Journal of Molecular... Feb 2024In recent years, the relationship between the microbiota and various aspects of health has become a focal point of scientific investigation. Although the most studied... (Review)
Review
In recent years, the relationship between the microbiota and various aspects of health has become a focal point of scientific investigation. Although the most studied microbiota concern the gastrointestinal tract, recently, the interest has also been extended to other body districts. Female genital tract dysbiosis and its possible impact on pathologies such as endometriosis, polycystic ovary syndrome (PCOS), pelvic inflammatory disease (PID), and gynecological cancers have been unveiled. The incursion of pathogenic microbes alters the ecological equilibrium of the vagina, triggering inflammation and compromising immune defense, potentially fostering an environment conducive to cancer development. The most common types of gynecological cancer include cervical, endometrial, and ovarian cancer, which occur in women of any age but especially in postmenopausal women. Several studies highlighted that a low presence of lactobacilli at the vaginal level, and consequently, in related areas (such as the endometrium and ovary), correlates with a higher risk of gynecological pathology and likely contributes to increased incidence and worse prognosis of gynecological cancers. The complex interplay between microbial communities and the development, progression, and treatment of gynecologic malignancies is a burgeoning field not yet fully understood. The intricate crosstalk between the gut microbiota and systemic inflammation introduces a new dimension to our understanding of gynecologic cancers. The objective of this review is to focus attention on the association between vaginal microbiota and gynecological malignancies and provide detailed knowledge for future diagnostic and therapeutic strategies.
Topics: Female; Humans; Genital Neoplasms, Female; Genitalia, Female; Ovarian Neoplasms; Microbiota; Inflammation
PubMed: 38396914
DOI: 10.3390/ijms25042237 -
European Urology Mar 2024Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment...
CONTEXT
Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment approaches often considered in advanced disease.
OBJECTIVE
To assess the clinical effectiveness of treatment options available for the management of inguinal and pelvic lymphadenopathy in men with penile cancer.
EVIDENCE ACQUISITION
EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews, and other databases were searched from 1990 to July 2022. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), and case series (CSs) were included.
EVIDENCE SYNTHESIS
We identified 107 studies, involving 9582 patients from two RCTs, 28 NRCSs, and 77 CSs. The quality of evidence is considered poor. Surgery is the mainstay of LN disease management, with early inguinal LN dissection (ILND) associated with better outcomes. Videoendoscopic ILND may offer comparable survival outcomes to open ILND with lower wound-related morbidity. Ipsilateral pelvic LN dissection (PLND) in N2-3 cases improves overall survival in comparison to no pelvic surgery. Neoadjuvant chemotherapy in N2-3 disease showed a pathological complete response rate of 13% and an objective response rate of 51%. Adjuvant radiotherapy may benefit pN2-3 but not pN1 disease. Adjuvant chemoradiotherapy may provide a small survival benefit in N3 disease. Adjuvant radiotherapy and chemotherapy improve outcomes after PLND for pelvic LN metastases.
CONCLUSIONS
Early LND improves survival in nodal disease in penile cancer. Multimodal treatments may provide additional benefit in pN2-3 cases; however, data are limited. Therefore, individualised management of patients with nodal disease should be discussed in a multidisciplinary team setting.
PATIENT SUMMARY
Spread of penile cancer to the lymph nodes is best managed with surgery, which improves survival and has curative potential. Supplementary treatment, including the use of chemotherapy and/or radiotherapy, may further improve survival in advanced disease. Patients with penile cancer with lymph node involvement should be treated by a multidisciplinary team.
Topics: Humans; Male; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Penile Neoplasms
PubMed: 37208237
DOI: 10.1016/j.eururo.2023.04.018 -
Archivio Italiano Di Urologia,... Jul 2023Primary sarcoma of the urinary bladder (SUB) is a rare but aggressive form of bladder cancer (BCa). Available evidence on SUB is limited to case reports and small...
PURPOSE OR OBJECTIVE
Primary sarcoma of the urinary bladder (SUB) is a rare but aggressive form of bladder cancer (BCa). Available evidence on SUB is limited to case reports and small series. The aim of the present multi-institutional study was to assess the clinical features, treatments, and outcomes of patients with SUB.
MATERIALS AND METHODS
Using a standardized database, 7 institutions retrospectively collected the demographics, risk factors, clinical presentation, treatment modalities and follow-up data on patients with SUB between January 1994 and September 2021. The main inclusion criteria included BCa with soft tissue tumor histology and sarcomatoid differentiation.
RESULTS
Fifty-three patients (38 men and 15 women) were identified. Median follow-up was 18 months (range 1-263 months). Median age at presentation was 69 years (range 16-89 years). Twenty-six percent of patients had a prior history of pelvic radiotherapy (RT), and 37% were previous smokers. The main presenting symptoms at diagnosis were hematuria (52%), pelvic pain (27%), and both hematuria and pelvic pain (10%). American Joint Committee on Cancer (AJCC) 8 th edition stage II, III and IV at diagnosis were 21%, 63% and 16%, respectively. Treatment modalities included surgery alone (45%), surgery plus neo- or adjuvant-chemotherapy (17%), surgery plus neo- or adjuvant-RT (11%), RT with concurrent chemotherapy (4%), neo-adjuvant chemotherapy plus surgery plus adjuvant RT (2%) and palliative treatment (21%). Rates of local and distant recurrences were 49% and 37%, respectively. Five-year overall survival and progression-free survival (PFS) were 66.5% and 37.6%, respectively. No statistically significant differences in PFS between the treatment modalities were observed.
CONCLUSIONS
Primary SUB is a heterogeneous disease group, commonly presenting at advanced stages and exhibiting aggressive disease evolution. In contrast to urothelial carcinoma, the primary pattern of recurrence of SUB is local, suggesting the need for multimodal approaches. Continuous international collaborative efforts seem warranted to provide guidance on how to best tailor treatments based on SUB-specific indices.
Topics: Male; Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Urinary Bladder Neoplasms; Urinary Bladder; Carcinoma, Transitional Cell; Hematuria; Retrospective Studies; Pelvic Neoplasms; Sarcoma; Soft Tissue Neoplasms; Pelvic Pain; Neoplasm Recurrence, Local
PubMed: 37491942
DOI: 10.4081/aiua.2023.11533 -
Cellular & Molecular Biology Letters Oct 2023The mitochondrial gene MCCC2, a subunit of the heterodimer of 3-methylcrotonyl-CoA carboxylase, plays a pivotal role in catabolism of leucine and isovaleric acid. The...
BACKGROUND
The mitochondrial gene MCCC2, a subunit of the heterodimer of 3-methylcrotonyl-CoA carboxylase, plays a pivotal role in catabolism of leucine and isovaleric acid. The molecular mechanisms and prognostic value still need to be explored in the context of specific cancers, including colorectal cancer (CRC).
METHODS
In vitro and in vivo cell-based assays were performed to explore the role of MCCC2 in CRC cell proliferation, invasion, and migration. Mitochondrial morphology, membrane potential, intracellular reactive oxygen species (ROS), telomerase activity, and telomere length were examined and analyzed accordingly. Protein complex formation was detected by co-immunoprecipitation (CO-IP). Mitochondrial morphology was observed by transmission electron microscopy (TEM). The Cancer Genome Atlas (TCGA) CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the MCCC2 expression level. The association between MCCC2 expression and various clinical characteristics was analyzed by chi-square tests. CRC patients' overall survival (OS) was analyzed by Kaplan-Meier analysis.
RESULTS
Ectopic overexpression of MCCC2 promoted cell proliferation, invasion, and migration, while MCCC2 knockdown (KD) or knockout (KO) inhibited cell proliferation, invasion, and migration. MCCC2 KD or KO resulted in reduced mitochondria numbers, but did not affect the gross ATP production in the cells. Mitochondrial fusion markers MFN1, MFN2, and OPA1 were all upregulated in MCCC2 KD or KO cells, which is in line with a phenomenon of more prominent mitochondrial fusion. Interestingly, telomere lengths of MCCC2 KD or KO cells were reduced more than control cells. Furthermore, we found that MCCC2 could specifically form a complex with telomere binding protein TRF2, and MCCC2 KD or KO did not affect the expression or activity of telomerase reverse transcriptase (TERT). Finally, MCCC2 expression was heightened in CRC, and patients with higher MCCC2 expression had favorable prognosis.
CONCLUSIONS
Together, we identified MCCC2 as a novel mediator between mitochondria and telomeres, and provided an additional biomarker for CRC stratification.
Topics: Humans; Colorectal Neoplasms; Telomere; Oncogenes; Mitochondria; Kaplan-Meier Estimate; Cell Proliferation; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Cell Movement
PubMed: 37828426
DOI: 10.1186/s11658-023-00487-0 -
Journal of Obstetrics and Gynaecology :... Dec 2023Aberrant Septin9 methylation in cervical cancer has been rarely studied. We aimed to identify its diagnostic value in cervical cancer using cervical scrapings, and its...
Aberrant Septin9 methylation in cervical cancer has been rarely studied. We aimed to identify its diagnostic value in cervical cancer using cervical scrapings, and its predictive potential in plasma for pelvic nodal metastasis of cervical cancer. The statuses of methylated Septin9 in fresh cervical lesions and cervical scrapings were first evaluated by using quantitative methylation-specific PCR. Subsequently, the relationship between Septin9 methylation in 113 plasma samples and pelvic nodal metastasis of cervical cancer was evaluated. Methylated Septin9 was detected in all cancerous tissues, but not in cervicitis. The degrees of Septin9 methylation increased with growing severity of cervical lesions in cervical scrapings. The sensitivity of methylated Septin9 was lower than that of cytology, while it yielded a high specificity and area under the curve in detecting high-grade squamous intraepithelial lesion or cervical cancer; and when Septin9 methylation combined with HPV16/18 genotyping, the sensitivity would increase from 70.42% to 82.39%. Plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%. In conclusion, we demonstrated methylated Septin9 to be an innovative diagnostic biomarker for cervical cancer and its non-invasive predictive potential in plasma for pelvic nodal metastasis of cervical cancer.Impact statement The occurrence of cervical cancer is related to Septin9 methylation. In fresh specimens and cervical scrapings, we found the degrees of methylated Septin9 increased with growing severity of cervical lesions. Compared with HPV16/18 genotyping and cytological detection, Septin9 methylation had a better specificity and AUC in detecting ≥ HSIL. Furthermore, plasma-based Septin9 methylation also had a high specificity for pelvic lymphatic metastasis prediction. Methylation analysis of Septin9 indicated a similar sensitivity, specificity and AUC in detecting ≥ HSIL, relative to HPV16/18 genotyping. Compared with cytological method, Septin9 methylation also yielded a higher specificity and AUC in detecting ≥ HSIL. And we also found plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%; additionally an increasing sensitivity from 50% to nearly 80% was found when combined with SCCAg. This study aimed to evaluate the relationship between Septin9 methylation and cervical cancer, and to explore the value of methylated Septin9 in the detection of cervical (pre)cancerous lesions. Moreover, we would explore plasma-based ctDNA biomarkers for pelvic lymphatic metastasis prediction of cervical cancer, to improve non-invasive predictive accuracy of pelvic nodal metastasis and reduce the complications caused by pelvic lymphadenectomy.
Topics: Female; Humans; Uterine Cervical Neoplasms; DNA Methylation; Human papillomavirus 16; Lymphatic Metastasis; Human papillomavirus 18; Biomarkers, Tumor; Uterine Cervical Dysplasia; Sensitivity and Specificity; Papillomavirus Infections
PubMed: 36476308
DOI: 10.1080/01443615.2022.2151356