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Journal of Cancer Research and Clinical... Feb 2024In some patients with prostate cancer, bone marrow carcinomatosis develops later in the course of the disease, which has a poor prognosis. These are often heavily...
PURPOSE
In some patients with prostate cancer, bone marrow carcinomatosis develops later in the course of the disease, which has a poor prognosis. These are often heavily pretreated patients in the castration-resistant situation for whom there are no other therapeutic options, because either all available systemic therapies have already been used or the use of one is not possible due to the cytopenias associated with bone marrow carcinomatosis. In our literature search, there are no data on this treatment in the setting available, especially no clinical trial or even randomized data. This case series is to determine the clinical efficacy of metronomic cyclophosphamide in patients with metastatic castration-resistant prostate cancer and bone marrow carcinomatosis, particularly with regard to stabilization of the blood count (thrombocytopenias) and thus the possibility of further (more toxic) lines of therapy.
METHODS
Retrospective unicenter analysis was performed on eleven patients between 54 and 84 years of age on metronomic cyclophosphamide for bone marrow carcinomatosis in metastatic castration-resistant prostate cancer treated at a Swiss cancer center between 2014 and 2023.
RESULTS
Eleven patients received metronomic cyclophosphamide for varying periods of time; the majority had severe cytopenias (especially thrombocytopenias). Partially hematologic stabilization was achieved with administration of further systemic therapies.
CONCLUSION
Our case series demonstrates that the use of metronomic cyclophosphamide allows hematologic stabilization for months, benefiting patients who had already received all available therapies for metastatic castration-resistant prostate cancer. Alternatively, it may act as bridging therapy to allow consecutive administration of more toxic therapies with proven survival benefit.
Topics: Humans; Male; Bone Marrow; Cyclophosphamide; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Thrombocytopenia; Middle Aged; Aged; Aged, 80 and over; Bone Marrow Neoplasms
PubMed: 38329600
DOI: 10.1007/s00432-023-05525-0 -
Journal of Oral Biology and... 2023The PTGS2 gene codes for the cyclooxygenase-2 (COX-2) enzyme that catalyzes the committed step in prostaglandin (PG) synthesis. Various and data suggest that...
Prostaglandin-endoperoxide synthase 2 (PTGS2) gene expression and its association with genes regulating the VEGF signaling pathway in head and neck squamous cell carcinoma.
INTRODUCTION
The PTGS2 gene codes for the cyclooxygenase-2 (COX-2) enzyme that catalyzes the committed step in prostaglandin (PG) synthesis. Various and data suggest that prostaglandin E2 mediates as a signaling molecule for activating the VEGF signaling pathway (VSP), forming an association between COX-2 and VSP. Several chemotherapy regimens increasingly rely on preventing the synthesis of PGs. The targeted and metronomic chemotherapy agents, which suppress the COX-2 enzymes, have a major role in suppressing the oral cancer cascade. Hence, this study was designed to understand the pattern of PTGS2 expression and genes regulating VSP in head and neck cancers.
METHODS
PTGS2 expression was analyzed in the TCGA database computationally with the help of the UALCAN web-server. The expression of VEGF signaling pathway genes was mined, and their expression pattern was determined. Co-expression analysis was done to elucidate the association between VEGF signaling genes and PTGS2. The ShineyGo web server was used for gene set enrichment.
RESULTS
Significantly high PTGS2 expression was observed in tumor samples. Further genes regulating VEGF signaling were significantly overexpressed in tumor samples. Co-expression analysis results showed a significant positive correlation between PTGS2 and angiogenesis-regulating genes. The majority of the genes were enriched for angiogenesis pathways.
CONCLUSION
PTGS2 was significantly expressed in head and neck cancer, and its expression was associated with genes regulating angiogenesis.
PubMed: 37559688
DOI: 10.1016/j.jobcr.2023.07.002 -
American Journal of Cancer Research 2024Distant metastasis is an important prognostic factor for oral squamous cell carcinoma (OSCC). It involves the direct spread of tumor cells through blood vessels or via...
Distant metastasis is an important prognostic factor for oral squamous cell carcinoma (OSCC). It involves the direct spread of tumor cells through blood vessels or via lymph nodes; however, there are currently no well-established treatments for its prevention in patients with OSCC. To investigate the impact of metronomic neoadjuvant chemotherapy on OSCC, we conducted a retrospective analysis of the efficacy of neoadjuvant chemotherapy with S-1 alone. Fifty-four patients underwent up-front surgery, while 106 received neoadjuvant chemotherapy with S-1 alone. A serious adverse event occurred in one of patient treated with neoadjuvant chemotherapy (1%); however, all patients underwent resection. The 5-year overall survival rate was higher with S-1 than with up-front surgery (96% vs. 81%, P = 0.002). Moreover, neoadjuvant chemotherapy significantly increased the overall survival rate of patients with poorly or moderately differentiated tumors, but not those with well-differentiated tumors. By analyzing a cohort of 523 head and neck squamous cell carcinoma (HNSCC) patients in the Cancer Genome Atlas, we identified genetic variants associated with histological differentiation. The frequency of pathogenic/likely pathogenic variants or deletions in 5 genes associated with HNSCC correlated with histological differentiation, some of which indicated the activation of the Wnt/β-catenin pathway in well-differentiated HNSCC. The vessel marker CD31 was highly expressed in poorly differentiated OSCC, whereas the anti-angiogenic molecule, LCN2, which is induced by the activation of the Wnt pathway, was highly expressed in well-differentiated OSCC. The present study showed that overall survival rates were higher in patients with poorly or moderately differentiated OSCC who received metronomic neoadjuvant chemotherapy, which was attributed to a difference in angiogenesis based on the characteristic landscape of pathogenic mutations according to histological differentiation.
PubMed: 38590400
DOI: 10.62347/EYNT8387 -
Cell Reports. Medicine Jun 2024Solid tumor pathology, characterized by abnormalities in the tumor microenvironment (TME), challenges therapeutic effectiveness. Mechanical factors, including increased... (Review)
Review
Solid tumor pathology, characterized by abnormalities in the tumor microenvironment (TME), challenges therapeutic effectiveness. Mechanical factors, including increased tumor stiffness and accumulation of intratumoral forces, can determine the success of cancer treatments, defining the tumor's "mechanopathology" profile. These abnormalities cause extensive vascular compression, leading to hypoperfusion and hypoxia. Hypoperfusion hinders drug delivery, while hypoxia creates an unfavorable TME, promoting tumor progression through immunosuppression, heightened metastatic potential, drug resistance, and chaotic angiogenesis. Strategies targeting TME mechanopathology, such as vascular and stroma normalization, hold promise in enhancing cancer therapies with some already advancing to the clinic. Normalization can be achieved using anti-angiogenic agents, mechanotherapeutics, immune checkpoint inhibitors, engineered bacterial therapeutics, metronomic nanomedicine, and ultrasound sonopermeation. Here, we review the methods developed to rectify tumor mechanopathology, which have even led to cures in preclinical models, and discuss their bench-to-bedside translation, including the derivation of biomarkers from tumor mechanopathology for personalized therapy.
PubMed: 38944037
DOI: 10.1016/j.xcrm.2024.101626 -
Molecular Cancer Feb 2024Soft tissue sarcomas (STS) are diverse mesenchymal tumors with few therapeutic options in advanced stages. Trabectedin has global approval for treating STS patients...
Soft tissue sarcomas (STS) are diverse mesenchymal tumors with few therapeutic options in advanced stages. Trabectedin has global approval for treating STS patients resistant to anthracycline-based regimens. Recent pre-clinical data suggest that trabectedin's antitumor activity extends beyond tumor cells to influencing the tumor microenvironment (TME), especially affecting tumor-associated macrophages and their pro-tumoral functions. We present the phase I/II results evaluating a combination of metronomic trabectedin and low-dose cyclophosphamide on the TME in patients with advanced sarcomas. 50 patients participated: 20 in phase I and 30 in phase II. Changes in the TME were assessed in 28 patients using sequential tumor samples at baseline and day two of the cycle. Treatment notably decreased CD68 + CD163 + macrophages in biopsies from tumor lesions compared to pre-treatment samples in 9 of the 28 patients after 4 weeks. Baseline CD8 + T cell presence increased in 11 of these patients. In summary, up to 57% of patients exhibited a positive immunological response marked by reduced M2 macrophages or increased CD8 + T cells post-treatment. This positive shift in the TME correlated with improved clinical benefit and progression-free survival. This study offers the first prospective evidence of trabectedin's immunological effect in advanced STS patients, highlighting a relationship between TME modulation and patient outcomes.This study was registered with ClinicalTrial.gov, number NCT02406781.
Topics: Humans; Trabectedin; Prospective Studies; Antineoplastic Agents, Alkylating; Sarcoma; Cyclophosphamide; Dioxoles; Tumor Microenvironment
PubMed: 38374062
DOI: 10.1186/s12943-024-01942-y -
Breast Cancer (Dove Medical Press) 2024Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only... (Clinical Trial)
Clinical Trial
Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.
PURPOSE
Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not.
PATIENTS AND METHODS
We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes.
RESULTS
All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06).
CONCLUSION
This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.
PubMed: 38628818
DOI: 10.2147/BCTT.S447290 -
Frontiers in Pharmacology 2024Targeted chemotherapy and immune checkpoint inhibitors (ICPi) have expanded the spectrum of therapies for patients with relapsed/refractory (r/r) Hodgkin's disease and...
Targeted chemotherapy and immune checkpoint inhibitors (ICPi) have expanded the spectrum of therapies for patients with relapsed/refractory (r/r) Hodgkin's disease and significantly improved the proportion of patients with long-term disease control. However, there is no standardized therapeutic option in case of further progression. Recently, we demonstrated that therapy with MEPED (metronomic chemotherapy, everolimus, pioglitazone, etoricoxib, dexamethasone) is highly effective in patients with r/r Hodgkin's disease. The benefit after pre-treatment with ICPi has not been studied, yet. Here, we report a patient with progressive Hodgkin's disease on Pembrolizumab for the first time who achieved sustained complete remission (CR) after initiation of MEPED therapy. A 57-year-old patient was pre-treated with brentuximab vedotin for relapsed advanced Hodgkin's disease and had received Pembrolizumab for progression from November 2020 to July 2022. Due to further progression, MEPED therapy was started in August 2022 and continued until May 2023. It consisted of a strictly oral daily (28-day cycle) application of low-dose treosulfan 250 mg, everolimus 15 mg, pioglitazone 45 mg, etoricoxib 60 mg, and dexamethasone 0.5 mg. Treatment response was evaluated by F-18 FDG-PET/CT (PET/CT). CR was defined by a negative Deauville score (DS) of 1-3. Already 3 months after starting MEPED, a CR (DS: 3) was confirmed by PET/CT in November 2022. The next follow-up in May 2023 continued to show CR (DS: 3). The therapy was very well tolerated. No hematological or other organ toxicity was observed. However, in May 2023 the patient presented with leg edema and weight gain, most likely due to pioglitazone and the PET/CT revealed suspected everolimus-induced pneumonitis, so MEPED was discontinued and diuretic therapy and treatment with prednisolone was started with gradual dose reduction. This resulted in a rapid complete resolution of the symptoms. The next PET-CT in July 2023 continued to show CR (DS: 3) without evidence of pneumonitis. Currently, therapy with MEPED has not been resumed. In conclusion, we demonstrate for the first time that MEPED therapy is highly effective in a patient with Hodgkin's disease who has been refractory to ICPi. Sustained CR was achieved over 11 months after initiation of MEPED therapy. Further studies on a larger patient cohort should be performed.
PubMed: 38444946
DOI: 10.3389/fphar.2024.1334233 -
Wounds : a Compendium of Clinical... May 2024Marjolin ulcer (MU) is an aggressive cutaneous malignancy that commonly occurs in those with a chronic wound such as post-burn scar. (Review)
Review
BACKGROUND
Marjolin ulcer (MU) is an aggressive cutaneous malignancy that commonly occurs in those with a chronic wound such as post-burn scar.
CASE REPORT
A 20-year-old male who sustained a flame burn over the scalp at 3 months of age developed a nonhealing ulcer over the burn scar 20 years later, which was treated with adequate surgical margins with adjuvant mold brachytherapy. Two months after completion of that treatment, he developed parotid nodal metastasis with positron emission tomography (PET)-positive bilateral cervical, supraclavicular, right suboccipital, and mesenteric lymph nodes that were treated with concurrent chemoradiation. One month later, the patient developed an ulcerative lesion involving the left parotid region with PET showing infiltration of the parotid gland, but with resolution of other previous sites of uptake. The patient was treated surgically with radical parotidectomy with elective neck dissection and reconstruction with locoregional flap. At 6-month follow-up, the patient developed extensive locoregional recurrence and distant metastasis and was started on oral metronomic therapy. The patient was alive with stable disease at 3-month follow-up after initiation of palliative chemotherapy.
CONCLUSION
Despite timely multimodality therapy, MU may present with a hostile clinical course with a short disease-free interval and early recurrence.
Topics: Humans; Male; Brachytherapy; Burns; Combined Modality Therapy; Neck Dissection; Neoplasm Recurrence, Local; Parotid Neoplasms; Plastic Surgery Procedures; Scalp; Skin Neoplasms; Skin Ulcer; Treatment Outcome; Adult
PubMed: 38861212
DOI: 10.25270/wnds/23138 -
European Journal of Obstetrics &... Jun 2024Recurrence rates of FIGO stage IB-IIA and IIB-IVA cervical cancer 28-64 respectively. There is a scarcity of data on the recurrence recurrence pattern for unusual...
To study the survival outcomes of uncommon recurrences among patients with cervical cancer compared with loco-regional and nodal recurrences at a tertiary care center in North East India - Bridging the knowledge gap in the existing literature.
BACKGROUND
Recurrence rates of FIGO stage IB-IIA and IIB-IVA cervical cancer 28-64 respectively. There is a scarcity of data on the recurrence recurrence pattern for unusual sites and theirrecurrence pattern for unusual sites and its association with survival and prognosis.
OBJECTIVE
To study overall survival in patients with distant metastasis compared to local and regional nodal metastasis.
METHODS
A retrospective study was done from 1/1/2017 to 30/12/22. Cervical cancer patients post primary treatments were included. Survival was analyzed with respect to 3 groups local, regional nodalconducted from 1/1/2017 to 30/12/22. Cervical cancer patients who had received primary post-primary treatments were included. Survival was analyzed with respect to three groups: local, regional nodal, and distant metastasis.
RESULTS
225 patients had recurrences post-completion of primary treatment, of which 105 (46.6%)(46.6 %) had local, 46 (20.4%)(20.4 %) had regional nodal, and 74 (33.3 %) had distant recurrences. The median time for recurrence in local, regional nodal, and atypical recurrences were 9, 9, and 13 months (p value - <0.05), respectively. Treatment included systemic chemotherapy 122 (54.2 %), metronomic therapy 19 (8.4 %), palliative radiotherapy 44 (19.5 %), palliative surgery 8 (3.5 %) and best supportive care 30 (13.3 %) patients. Median Time to treatment-death of patients after recurrence in local, nodal and distant recurrences was 17.0 months, 18.0 months and 10.0 months respectively (p value - < 0.05). Overall Survival of patients after primary treatment with local, nodal and distant recurrences was 35.0 months, 47.0 months and 50.0 months respectively (p value <0.05).
CONCLUSION
Local recurrence is most common, followed by regional, nodal, and distant recurrences. Overall survival post recurrence was lowest for distant recurrences and highest for local recurrences however overall survival after primary treatment completion was highest for distant recurrence due to the late presen; however, tation of distant recurrences.
PubMed: 38770162
DOI: 10.1016/j.eurox.2024.100314 -
Cureus Sep 2023Leptomeningeal carcinomatosis (LC) is an uncommon sequelae of metastatic cancer affecting the pia and arachnoid mater. It has been postulated that recent improvements...
Leptomeningeal carcinomatosis (LC) is an uncommon sequelae of metastatic cancer affecting the pia and arachnoid mater. It has been postulated that recent improvements in cancer patient survival time have increased the frequency of LC and other rare metastatic conditions that patients previously would not have lived long enough to experience. LC carries a universally poor prognosis with a mean survival of between two to four months if treated; however, the recent increase in incidence has allowed for further research into the condition and potential treatments. Options for administering chemotherapy have been limited in the past, but recent developments in surgical chemotherapeutic ports have allowed for intrathecal delivery of drugs like methotrexate without systemic exposure. In fact, innovative delivery systems undergoing clinical trials can deliver these drugs in a metronomic fashion to limit the leukoencephalopathy complications of methotrexate. Primary breast cancer is the most common source of metastatic leptomeningeal lesions, and such a lesion was observed by the authors in the cadaver of a 70-year-old Caucasian female with unspecified breast cancer in a medical school anatomic laboratory. The cause of death was listed as "complication of malignant neoplasm of unspecified site of unspecified female breast." Through this case report, we seek to develop our understanding of this rare metastatic phenomenon and highlight the importance of student cadaveric dissection.
PubMed: 37790014
DOI: 10.7759/cureus.44533