Paclitaxel Regimen Research Articles

Scalp cooling therapy for chemotherapy-induced hair loss in patients with breast or gynecological cancers-an Asian tertiary institution experience.

Scalp cooling therapy (SCT) improves chemotherapy-induced alopecia (CIA), but there are few published data about its efficacy in an Asian-predominant population. We report our tertiary institution experience of SCT in patients with breast or gynaecological cancers undergoing chemotherapy. The Paxman scalp cooling system was employed for eligible women with breast or gynaecological cancers receiving anthracycline or taxane-based chemotherapy. Only patients with Grade (G) 0-1 alopecia by common terminology criteria for adverse events (CTCAE) version 4.0 were eligible initially, but patients with G2 alopecia were later included in the study. SCT was performed at each chemotherapy cycle, commencing 30min prior to and continuing up to 90min after completion of the drug infusion. Patients were assessed at the start and end of each session for hair preservation (defined as G0-2 alopecia) and comfort level of SCT (rated on a 5-point visual scale). The primary end point was success of hair preservation or hair regrowth after completion of all cycles of chemotherapy. Eighty-three patients were enrolled over a period of 18months from December 2017 to October 2019, with a total of 510 scalp cooling cycles performed. 94.0% (n = 78) of patients reported a comfort score of 3 and above, indicating that the procedure was comfortable, upon a 5-point visual scale. Patients receiving weekly paclitaxel had highest success in hair preservation at 76.7% (23/30 patients), with a lower rate of hair preservation observed for the 3 weekly paclitaxel regimen (50%, 2/4 patients). In contrast, only 1 patient (5.3%, 1/19 patients) who underwent chemotherapy with anthracycline and cyclophosphamide achieved hair preservation. SCT is well tolerated in an Asian-predominant population. Among women with breast or gynaecological cancers receiving taxane and/or anthracycline based chemotherapy, those who underwent SCT were about 50% more likely to achieve hair preservation or hair regrowth, as compared to historical controls.

Utility of atezolizumab plus bevacizumab, carboplatin, and paclitaxel combination for the treatment of advanced non-squamous non-small cell lung cancer patients with malignant pleural effusion.

Malignant pleural effusion (MPE) remains a negative prognostic factor in non-small cell lung cancer (NSCLC), even after the emergence of immune checkpoint inhibitors. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Bevacizumab, a humanized monoclonal antibody against VEGF, is a key agent for patients who develop MPE. However, it is unclear whether MPE is a poor prognostic factor in patients with advanced non-squamous NSCLC receiving treatment with the atezolizumab plus bevacizumab, carboplatin, and paclitaxel (ABCP) regimen. Moreover, the effect of ABCP on MPE control is unknown. This study aimed to elucidate the efficacy and safety of ABCP for non-squamous NSCLC patients with MPE. We retrospectively analyzed consecutive patients with advanced non-squamous NSCLC who received treatment with ABCP (January 2019-September 2023). Patients were divided into two groups (non-MPE and MPE), and treatment outcomes were compared. In the MPE group, treatment efficacy for MPE control and toxicity were evaluated. Of the 46 patients enrolled, 17 and 29 were included in the non-MPE and MPE groups, respectively. The objective response and disease control rates were not significantly different between the non-MPE and MPE groups (76.5% vs. 51.7%, P=0.13; 88.2% vs. 82.8%, P>0.99; respectively). Similarly, the median progression-free survival and median overall survival were not significantly different (9.9 vs. 10.1 months, P=0.87; 16.0 vs. 19.9 months, P=0.87, respectively). In the MPE group, 25 patients (86.2%) achieved MPE control lasting >8 weeks from the initiation of treatment with ABCP; the median progression-free survival without an unequivocal increase in MPE was 15.0 months. The incidence rates of grade ≥3 non-immune- and immune-related adverse events were 83% and 17%, respectively. There was no treatment-related death. The ABCP regimen may be a promising treatment option for non-squamous NSCLC patients with MPE.

Comparison of Weekly Paclitaxel Regimens in Recurrent Platinum-Resistant Ovarian Cancer: A Single Institution Retrospective Study.

Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better tolerability profile without compromising efficacy.

Successful treatment of PD1-inhibitor induced psoriasiform dermatitis using IL-17 blockade without compromising immunotherapy efficacy.

Pembrolizumab is a monoclonal PD-1 inhibitor used in the treatment of lung cancer in addition to several other malignancies. Psoriasiform dermatitis is a well-documented adverse effect. We present a 68 year-old-male with a 50-year smoking history and a 30-year remote history of plaque psoriasis, limited to the knees and elbows, who presented with metastatic non-small cell lung cancer. He was started on a chemotherapy regimen of carboplatin, paclitaxel, and pembrolizumab. One month later, he presented to dermatology with diffuse erythematous scaly papules coalescing into plaques on 80% of body surface area (BSA). Pembrolizumab treatment was paused. The patient was prescribed triamcinolone 0.1% twice daily, but still had significant BSA at one-month and was started on an Il-17 inhibitor, ixekizumab, clearing the psoriasiform dermatitis. He was rechallenged with pembrolizumab every 3 weeks and repeat PET/CT demonstrated excellent tumor response. This case prompted a literature review to further characterize the use of IL-17 inhibitors for psoriasiform dermatitis in the setting of ICI therapy. All six cases demonstrated improvement of psoriasiform dermatitis, with two cases showing partial response and four cases showing complete resolution. In three of the six cases, the patients exhibited clinical response to the primary malignancy after rechallenging with ICI, while remaining on an IL-17 inhibitor. Our case, in conjunction with the other reported cases, seems to suggest that IL-17 blockade can maintain a fine balance in this challenging clinical scenario by treating psoriasiform dermatitis without compromising the efficacy of immunotherapy.

Persistent response to combination treatment of pemigatinib and chemotherapy in a patient with advanced gastric cancer: A case report

AbstractObjectiveThis study aimed to report the treatment and outcomes of a patient with advanced gastric cancer (GC) using a combination of a targeted molecular therapy and chemotherapy.Patients and methodsA 40‐year‐old woman presented with abdominal metastatic nodules and peritoneal effusion. Biopsy and cytology identified signet ring cell carcinoma. Ten months after the onset of initial symptoms, gastroscopy confirmed signet ring cell carcinoma of the gastric body. Genetic testing revealed amplification of the fibroblast growth factor receptor (FGFR) gene. Consequently, the patient received FGFR inhibitor pemigatinib in addition to a chemotherapy regimen of albumin paclitaxel plus 5‐fluorouracil.ResultsDuring the treatment, the patient experienced recurrent liver function abnormalities and intestinal obstruction, which were managed with symptom‐specific medications and supportive therapies. The combined treatment regimen resulted in a progression‐free survival (PFS) period of ten months.ConclusionThe integration of FGFR inhibitor pemigatinib with standard chemotherapy showed promising results in prolonging PFS in a patient with advanced GC characterized by FGFR gene amplification, despite the occurrence of manageable side effects.

Expert consensus recommendations on the daily clinical use of pembrolizumab for early triple-negative breast cancer.

e12521 Background: Triple-negative breast cancer (TNBC) accounts for 10–15% of all breast cancer cases and is associated with poor outcomes. Neoadjuvant chemotherapy is the standard treatment for early TNBC (eTNBC) to achieve a pathologic complete response which is associated with long-term clinical outcomes and to guide adjuvant treatment for residual disease after definitive surgery. Pembrolizumab, a programmed death 1 (PD-1) inhibitor, is approved for the peri-operative treatment of stage II and III TNBC. The Hong Kong Breast Cancer Foundation (HKBCF) convened a multi-disciplinary consensus consisting of surgeons, and clinical and medical oncologists to discuss the implementation of immunotherapy in the peri-operative setting and provide expert guidance on topics lacking definitive evidence from the KEYNOTE-522 study in daily clinical routine. Methods: The panel included 7 breast surgeons, 6 clinical oncologists, and 3 medical oncologists representing the academic, public, and private settings in Hong Kong. A modified Delphi panel was conducted, testing the panel on 7 different topics and 45 statements relating to the peri-operative treatment of eTNBC. Evidence was graded according to GRADE. Statements were initially voted by online form on a 6-point Likert scale, and the results were discussed during a consensus meeting. Consensus to accept was considered at a median ≥5 and an IQR ≤1.75 and consensus to reject at median ≤2 and an IQR ≤1.75. Results: Key findings are that the panel considered 1) the uncommon subtype “oestrogen receptor (ER)-low” does not formally meet the definition of TNBC but should be treated as TNBC; 2) pembrolizumab as a viable addition in the peri-operative setting; 3) guideline-recommended NAC for cT1c disease may be considered; but 4) this does not necessarily mean immunotherapy should be added, though it may be considered case-by-case. Furthermore, the panel 5) agreed that pembrolizumab prescription does not need to be guided by PD-L1 expression, and 6) that for patients with residual disease after NAC plus pembrolizumab, the addition of capecitabine to pembrolizumab is acceptable, however, 7) was divided about the addition of a PARPi to pembrolizumab for patients with a germline BRCA1/2 mutation (g BRCA1/2m) and residual disease — guided by the lack of routine g BRCA1/2m testing in Hong Kong. Finally, the panel 8) proposed to recommend adhering to the KEYNOTE-522 weekly paclitaxel regimen with a subclause to consider 3-weekly regimen as an alternative for specific technical or logistical challenges. Conclusions: The KEYNOTE-522 study has provided robust evidence on the efficacy and safety of peri-operative pembrolizumab in eTNBC patients. However, several clinical questions remain unanswered, and until further evidence is available, the HKBCF recommendations provide expert guidance on the use of pembrolizumab for eTNBC patients in daily clinical practice.

Systemic inflammatory markers in neoadjuvant pembrolizumab therapy for triple-negative breast cancer: Prognostic insights and nomogram construction.

e12649 Background: Systemic inflammatory markers derived from peripheral blood cells, such as the neutrophils and lymphocytes ratio (NLR), derived neutrophil lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), and lymphocyte–monocyte ratio (LMR), have shown promise as prognostic markers. Currently, neoadjuvant treatment (NACT) for early triple-negative breast cancer (eTNBC) involves the addition of an immune therapy, and little is known about the variation of these markers in this specific context. Methods: This study evaluated two groups who received NACT for eTNBC in a single third-level cancer center. The first received NACT with EC X4 and a weekly paclitaxel regimen, the second pembrolizumab and NACT. A total of 70 patients were included, 37 patients in the pembrolizumab group. NLR was defined as the absolute blood neutrophil count (N) divided by the absolute lymphocyte count (L), dNLR was defined as the N divided by the derived L (absolute leukocyte count — N), PLR was defined as the absolute platelet count divided by the L, LMR was defined as the L divided by the absolute monocyte count. Association between systemic inflammatory markers and pathological complete response (pCR) was analyzed using statistical tests. Inflammatory markers were evaluated at the time of diagnosis, at the time of chemotherapy regimen change, and 1 week before surgery. The χ2 test or Fisher’s exact test was used for correlation and Student’s t-test to compare different groups. Results: The pCR rates were 60,6% in the standard therapy and 77,8% in the pembrolizumab. There were no significant differences in clinical characteristics between the two groups. NLR, dNLR, PLR and LMR at 6 months showed significant differences compared to baseline levels. dNLR in the immunotherapy group, at the end of therapy, showed statistical significance with the Welch Two Sample t-test with p-value = 0.001. Variables were weighted with respect to the type of treatment and the outcome was assessed as pCR. On the basis of these data, a nomogram was constructed to predict the likelihood of achieving pCR in patients undergoing neoadjuvant pembrolizumab therapy. Conclusions: This study highlights the potential of systemic inflammatory markers as prognostic indicators in patients with eTNBC undergoing NACT. dNLR is a novel biomarker associated with clinical outcome in solid tumors. In this study, for the first time, a correlation was found between the use of pembrolizumab and the change in dNLR and consequently its impact on pCR. A nomogram was constructed to predict the outcome of pCR. [Table: see text]

Polymeric micellar paclitaxel plus cisplatin combined with tislelizumab as the first-line treatment of advanced unresectable esophageal squamous cell carcinoma: A phase II study.

e16022 Background: Immunotherapy combined with chemotherapy has become the standard first-line treatment for advanced and metastatic esophageal squamous cell carcinoma (ESCC). However, the prophylactic use of hormones, a routine preconditioning regimen of paclitaxel, may weaken the immune response. Polymeric micellar paclitaxel is a new formulation of paclitaxel without polyoxyethylene castor oil solvent, which do not need for pretreatment with anti-allergy drugs before administration. We aimed to evaluate the efficacy and safety of polymeric micellar paclitaxel (pm-Pac) plus cisplatin combined with tislelizumab for unresectable advanced ESCC. Methods: This is a single-center, single-arm, prospective phase II clinical trial. Stage IV ESCC patients diagnosed histologically or cytologically without systemic treatment are eligible for this study. Polymeric micellar paclitaxel plus cisplatin combined with tislelizumab was treated for 2 cycles. After imaging evaluation, if there was no disease progression, an additional two cycles of treatment were completed, followed by maintenance treatment with tislelizumab for one year. At day 1 of each therapy cycle, patients were given pm-Pac 230 mg/m2 followed by cisplatin 70 mg/m2 combined with tislelizumab 200 mg via intravenous infusion, every three weeks. This trial planned to include 30 patients. The primary endpoint was objective response rate (ORR) determined by the independent review committee. And the secondary endpoints included overall survival, progression-free survival evaluated based on the Response Evaluation Criteria in Solid Tumors (version 1.1), as well as the incidence and severity of adverse events. Results: From September 2022 to January 2024, 31 patients were included in the trial. Median age was 65 years, 29 (93.5%) patients were male. Median follow-up was 13.1 months, 2 patient achieved complete response (CR), 19 of them showed partial response (PR), 8 stable disease (SD), illustrating an ORR of 67.7% and a DCR of 93.5%. Median PFS was 7.3 months. The most common AEs were neutropenia (90.3%), nausea(83.8%) and thrombocytopenia (25.8%). No grade 3 or higher immune-related AE was observed, and there were no treatment-related deaths. Conclusions: The pm-Pac plus cisplatin combined with tislelizumab as first-line treatment of unresectable advanced ESCC showed effective without new safety signal. This combination therapy may have great efficacy, but multi-center randomized trials with larger sample size are warranted in further.

The Trends and Outcomes of Initial Palliative Chemotherapy in Patients with Pancreatic Cancer in Korea Based on National Health Insurance Service Data.

Background/Objectives: The survival rate of patients with pancreatic cancer (PC) has improved gradually since the introduction of FOLFIRINOX (FFX) and gemcitabine + albumin-bound paclitaxel (GnP) regimens. However, the trends and outcomes of initial palliative chemotherapy before and after the advent of these regimens and their contribution to survival rates are not well understood. This study aimed to investigate this in patients with PC in Korea using claims data from the National Health Insurance Service (NHIS). Methods: Patients diagnosed with PC who underwent initial palliative chemotherapy between 2007 and 2019 were identified from the NHIS database. Patient demographics, comorbidities, chemotherapy regimens, and survival rates were analyzed using follow-up data up to 2020. Results: In total, 14,760 patients (mean age, 63.78 ± 10.18 years; men, 59.19%) were enrolled. As initial palliative chemotherapy, 3823 patients (25.90%) received gemcitabine alone; 2779 (18.83%) received gemcitabine + erlotinib; 1948 (13.20%) received FFX; and 1767 (11.97%) received GnP. The median survival values were 15.00 months for FFX; 11.04 months for GnP; 8.40 months for gemcitabine alone; and 8.51 months for gemcitabine + erlotinib. The adjusted hazard ratio (aHR) for GnP vs. FFX was 1.291 (95% CI, 1.206-1.383) in the multivariate Cox regression analysis of mortality. Radiation therapy (aHR, 0.667; 95% CI, 0.612-0.728) and second-line chemotherapy (aHR, 0.639; 95% CI, 0.597-0.684) were significantly associated with improved survival. Conclusions: Our study found that first-line chemotherapy with FFX was associated with significantly longer survival than the other regimens, although caution is needed in interpreting the results.

Heterogeneous treatment effect of dose-dense paclitaxel plus carboplatin therapy for advanced ovarian cancer.

A Japanese clinical trial (JGOG3016) showed that dose-dense weekly paclitaxel in combination with carboplatin extensively prolonged overall survival (OS) in patients with advanced ovarian cancer. However, in other clinical trials, dose-dense paclitaxel regimens were not superior to triweekly paclitaxel regimens. In this study, causal tree analysis was applied to explore subpopulations with different treatment effects of dose-dense paclitaxel in a data-driven approach. The 587 participants with stage II-IV ovarian cancer in the JGOG3016 trial were used for model development. The primary endpoint was treatment effect in terms of 3-year OS in patients receiving dose-dense vs. conventional paclitaxel therapies. In patients <50 years, the 3-year OS was similar in both groups; however, it was higher in the dose-dense group in patients ≥50 years. Dose-dense paclitaxel showed strong positive treatment effects in patients ≥50 years with stage II/III disease, BMI <23 kg/m2, non-CC/MC, and residual tumor ≥1 cm. In contrast, although there was no significant difference in OS; the 3-year OS rate was 23% lower in dose-dense paclitaxel than conventional paclitaxel in patients ≥60 years with stage IV cancer. Patients in this group had a particularly lower performance status than other groups. Our causal tree analysis suggested that poor prognosis groups represented by residual tumor tissue ≥1 cm benefit from dose-dense paclitaxel, whereas elderly patients with advanced disease and low-performance status are negatively impacted by dose-dense paclitaxel. These subpopulations will be of interest to future validation studies. Personalized treatments based on clinical features are expected to improve advanced ovarian cancer prognosis.

Abstract PO3-14-04: Prognostic value of systemic inflammatory markers in neoadjuvant chemotherapy for breast triple negative cancer with pembrolizumab: development of a nomogram

Abstract Introduction: Systemic inflammatory markers derived from peripheral blood cells, such as the neutrophil-lymphocyte ratio (NLR), derived neutrophil-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), have shown promise as prognostic markers for various cancer types. Inflammation plays a crucial role in cancer development, progression, metastasis, and resistance to treatment. However, only a few preoperative biomarkers have been identified as independent prognostic markers. Systemic inflammatory markers offer a reliable and easily accessible approach for prognosis evaluation. Materials and Methods: This study evaluated two groups of patients who received neoadjuvant chemotherapy for triple-negative breast cancer outside of clinical trials. The first group underwent neoadjuvant chemotherapy in 2021 with the EC X4 and weekly paclitaxel regimen, whereas the second group received neoadjuvant chemotherapy in 2022 following the KEYNOTE-522 study protocol with pembrolizumab. A total of 44 patients were included, with 23 patients in the pembrolizumab group. The NLR was defined as the absolute blood neutrophil count divided by the absolute lymphocyte count, and the derived neutrophil/lymphocyte ratio (dNLR) was defined as the absolute neutrophil count divided by the derived lymphocyte count (absolute leukocyte count —neutrophil count). The PLR was defined as the absolute platelet count divided by the absolute lymphocyte count. The LMR was defined as the absolute lymphocyte count divided by the absolute monocyte count. The association between systemic inflammatory markers (NLR, dNLR, PLR, and LMR) and pathological complete response (pCR) was analyzed using statistical tests. Inflammatory markers were evaluated at the time of diagnosis, at the time of chemotherapy regimen change, and two weeks before surgery. The χ2 test or Fisher’s exact test was used to analyze the correlation between the inflammatory indices and clinicopathologic parameters. Student’s t-test was used to compare different groups of continuous parametric data. Results: The pCR rates were 67% in the standard therapy group and 87% in the pembrolizumab group. There were no significant differences in other clinical characteristics between the two groups. The NLR, dNLR, PLR, and LMR at 6 months showed statistically significant differences compared to baseline levels. This difference was more evident in patients undergoing pembrolizumab therapy. ROC curves for the pembrolizumab group demonstrated an area under the curve (AUC) of 0.737, indicating a strong correlation between these systemic inflammatory markers and pCR. Based on these data, a nomogram was constructed to predict the likelihood of achieving pCR in patients undergoing neoadjuvant pembrolizumab therapy. Conclusion: This study highlights the potential of systemic inflammatory markers as prognostic indicators in patients with TNBC undergoing neoadjuvant chemotherapy. The significant differences observed in the pembrolizumab group and the high AUC of the ROC curves suggest the utility of these markers in predicting treatment response. The developed nomogram provides a practical tool for clinicians to estimate the probability of pCR based on NLR, dNLR, PLR, and LMR. Further research and validation are required to confirm the clinical utility of these markers in larger patient cohorts. Nomogram –insert figure image– ROC curve –insert figure image– Citation Format: Filippo Giovanardi, Giancarlo Bisagni, Elisa Gasparini, Alessandra Bologna, Roberto Di Cicilia, Gabriella Moretti, Claudia Degli Esposti, Carmine Pinto. Prognostic value of systemic inflammatory markers in neoadjuvant chemotherapy for breast triple negative cancer with pembrolizumab: development of a nomogram [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-14-04.

Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer: a multicenter, open-label, non-inferiority, randomized controlled trial

BackgroundThe paclitaxel liposome formulation, encapsulating paclitaxel within a phospholipid bilayer, addresses the insolubility of traditional paclitaxel formulations, thereby reducing toxicity without compromising its antitumor efficacy. MethodsThis multicenter, open-label, non-inferiority randomized controlled trial (ChiCTR2000038555) evaluates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin (PLC vs. PC) as first-line therapy in patients with epithelial ovarian cancer. ResultsAn analysis of median progression-free survival (PFS) revealed non-inferior outcomes between 263 patients in the PLC group and 260 patients in the PC group (32.3 vs. 29.9 months, hazard ratio [HR], 0.89 [95% CI, 0.64−1.25]), using a non-inferior margin of 1.3. Although the overall incidence of treatment-related adverse events was comparable between groups, the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen. ConclusionThe findings affirm the non-inferiority of paclitaxel liposome compared to the combination of paclitaxel and carboplatin regarding therapeutic efficacy, with an enhanced safety profile marked by reduced non-hematologic toxicities.

Study on the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy regimen for III–IVA esophageal squamous cell carcinoma post-surgery

Background and aimsThe treatment of esophageal squamous cell carcinoma is still controversial, and neoadjuvant chemotherapy combined with immunotherapy is a hot topic of current research. We investigated the recent efficacy and surgical safety of patients with III–IVA esophageal squamous cell carcinoma after neoadjuvant regimen of paclitaxel + cisplatin/nedaplatin/carboplatin + sindilizumab, to provide a theoretical basis for evaluating the feasibility of surgery after neoadjuvant therapy.MethodsThe clinical data of patients with stage III–IVA esophageal squamous cell carcinoma admitted from January 2022 to April 2023 at our hospital were collected for retrospective analysis. The patients were divided into the neoadjuvant combination surgery group (34 patients with the regimen of paclitaxel + cisplatin/nedaplatin/carboplatin + sintilimab two/three cycles of preoperative neoadjuvant therapy) and surgery-only group (36 patients). Statistical analysis was performed to compare the differences between both groups particularly for intraoperative bleeding, operative time, incidence of postoperative pulmonary complications, laryngeal recurrent nerve injury, thoracic duct injury, anastomotic fistula, and postoperative hospital days. Additionally, the pCR/MPR rates of the neoadjuvant group were analysed.ResultsSignificant differences were present in the clinical and pathological staging before and after neoadjuvant treatment (P ≤ 0.001). The neoadjuvant group had a pCR rate of 26.47% and an ORR rate of 88.23%. No significant differences were discovered in R0 resection rate between both groups, as well as intraoperative bleeding, operative time, intraoperative laryngeal recurrent nerve injury rate, thoracic duct injury rate, postoperative anastomosis incidence, postoperative hospital days, and postoperative lung infection incidence (P > 0.05).ConclusionsThe neoadjuvant immune combination chemotherapy regimen had considerable tumor regression and pathological remission benefits, without reducing the safety of surgery, possibly presenting as a new treatment plan.

Immunotherapeutic options for management of metastatic cervical cancer

Cervical cancer (CC) remains one of the common tumour diseases of women. It accounts for 9.8% of all neoplasia in women. The Food and Drug Administration approved pembrolizumab with PD-1 inhibitor antibodies for the treatment of RSM following the KEYNOTE-158 clinical trial. PD-L1/PD-1 inhibitors have shown promising results against objective response rate in female patients with CC. A clinical case of pembrolizumab treatment of a patient with metastatic CC with progression after radiotherapy and pelvic organ evisceration is described. The patient underwent IHC examination of the tumour material and was found to have PDL1 expression of more than 1% according to the 22C3 antibody assay. According to the instructions for Pembroria® it was decided to start systemic chemotherapy in the regimen of paclitaxel 175 mg/m2, carboplatin AUC5 and pembrolizumab at a dose of 200 mg every three weeks. After the third course, a control MRI study was performed. A partial response according to iRECIST criteria was confirmed. After the sixth course of therapy cytostatics were cancelled, the patient continued monotherapy with pembrolizumab 200 mg once every three weeks. At the control MRI after 10 months of therapy, the tumour conglomerate in the right hindbrain fossa was not detected and a complete response was confirmed. In the given observation anti-PD1 therapy and metastatic CC allowed to achieve complete remission of the disease. Thus, the clinical observation demonstrates the efficacy of pembrolizumab therapy in patients with advanced CC.

Evaluation of Histomorphological Changes in Breast Cancer Post-Neoadjuvant Chemotherapy.

Breast cancer, a leading cause of global female mortality, demands comprehensive diagnostic and therapeutic strategies. This study delves into the nuanced realm of post-neoadjuvant chemotherapy breast cancer specimens, emphasizing the imperative need for pathologists to discern stromal and nuclear alterations adeptly. The investigation, encompassing 100 female patients with a mean age of 47.5years, elucidates the demographic and clinicopathological parameters. Predominantly presenting as palpable lumps (85%), invasive ductal carcinoma emerged as the predominant histological type (98%). The primary focus of the study revolves around the morphological changes post-neoadjuvant chemotherapy, with a meticulous qualitative analysis encompassing stromal elements (fibrosis, elastosis, calcification) and nuclear features (pyknosis, hyperchromasia). Notably, the response to chemotherapy, classified by the International Union against Cancer criteria, delineates a substantial pathological complete response (55%), partial response (35%), and limited non-response (10%). The therapeutic landscape includes a majority of cases undergoing extensive chemotherapy cycles, primarily featuring the cyclophosphamide, doxorubicin, and paclitaxel regimen. Remarkably, this investigation unveils fibrosis (63%) and elastosis/collagenization (51%) as prevalent stromal changes, while pyknosis (58%) and hyperchromasia (48%) dominate nuclear alterations. In conclusion, this retrospective study provides a comprehensive overview of post-neoadjuvant chemotherapy breast cancer specimens, shedding light on the intricate interplay of clinical parameters, treatment responses, and histopathological changes. The findings underscore the pivotal role of pathologists in accurately diagnosing and grading tumors in the evolving landscape of breast cancer management.

David Slays Goliath: Exceptional Efficacy of Oral Vinorelbine in Conquering Metastatic Finger Angiosarcoma

Abstract Angiosarcoma (AS) is a rare and aggressive disease originating from blood or lymphatic vessel endothelium, representing &lt;1% of soft-tissue sarcomas. The prognosis is generally poor, with a 5-year survival rate of only 30%–50%. The recurrence rate is high, and metastasis occurs in about half of the cases. The National Comprehensive Cancer Network guidelines recommend anthracycline-based, gemcitabine-based, and paclitaxel regimens as preferred first-line treatments for metastatic AS. Vinorelbine, a vinca alkaloid, is listed as supportive care in AS for patients unsuitable for intensive chemotherapy or who are heavily treated. Although the efficacy of vinorelbine is modest, some studies suggest its synergistic effect with immunotherapy. In our case report, a patient with metastatic AS received frontline paclitaxel followed by pembrolizumab, but this treatment failed. However, a complete response (CR) was achieved after oral vinorelbine. Remarkably, the patient remains in CR for 4.5 years after discontinuing vinorelbine.

High-grade serous ovarian carcinoma in a patient with end-stage renal disease

Introduction. Ovarian cancer, being one of the most common gynecologic cancers, has the highest mortality rate. The gold standard for the treatment of patients with advanced ovarian cancer, along with angiogenesis inhibitors applied in certain advanced stages, is cytoreductive surgery, followed by chemotherapy (CHT). The use of chemotherapeutic agents in hemodialysis (HD) patients has some specificities and limitations, and no CHT guidelines exist for treating those patients. Case report. We present a 45-year-old female patient with end-stage renal disease undergoing HD treatment. Abdominal and pelvic magnetic resonance imaging showed a multicystic mass with a total diameter of 93 ? 115 ? 168 mm in the right ovary and two subcapsular lesions in the VI segment of the liver with a diameter of 22 ? 14 mm and 9 mm (stage IVb ovarian cancer). The serum level of the tumor marker cancer antigen 125 (CA-125) was 93 U/mL. A total hysterectomy with bilateral salpingo-oophorectomy and infracolic omentectomy was performed. Histopathological analysis of the surgical specimen confirmed high-grade serous ovarian adenocarcinoma, FIGO stage IVb. After surgery, she was treated with carboplatin and paclitaxel combination CHT, determining the dose of carboplatin according to the Calvert formula and initiating HD within 20 hrs of infusion. Two years after the diagnosis was made, the presented patient is in good condition. Conclusion. HD patients can be treated with a combination CHT regimen of carboplatin and paclitaxel, determining the dose of carboplatin according to the Calvert formula and initiating HD within 20 hrs from the end of the chemotherapeutic infusion.

Study of long-term effects of pelvic radiotherapy on the function of bone marrow in recurrent cervical cancer patients.

Purpose: To study the effects of prior pelvic radiotherapy on bone marrow suppression in recurrent cervical cancer patients during chemotherapy. Methods and materials: The cases of 129 patients with recurrent cervical cancer were reviewed, of which 77 patients had pelvic radiotherapy history and another 52 patients with no pelvic radiotherapy history were used as control group. All patients received a chemotherapy regimen of paclitaxel combined with carboplatin (TC) per 21 days for 5-6 times. Hematologic toxicity, including count of red blood cell, white blood cell and neutrophil cell and platelet, was defined by using Common Terminology Criteria for Adverse Events (version 4.0). The relationship between age, body mass index, disease free survival, pathological types, FIGO stages, radiotherapy methods and the degree of bone marrow suppression during chemotherapy was statistically analyzed, respectively, for all recurrent cervical cancer patients. Results: Among 77 patients with previous radiotherapy history, 73 recurrent patients (94.8%) had bone marrow suppression followed by chemotherapy. Recurrent cervical cancer patients without prior radiotherapy (n=52) showed a lower risk of bone marrow suppression followed by chemotherapy (n=39, 75.0%, P < 0.05). The probability of severe bone marrow suppression (grade III-IV) after chemotherapy in recurrent cervical patients with or without history of radiotherapy was 41.6% and 13.5%, respectively (P < 0.05). In univariate analysis, radiotherapy methods were associated with the incidence of grade III-IV bone marrow suppression in recurrent cervical cancer patients (P=0.005). In multivariate analysis, radiotherapy methods and extended-field radiotherapy were the risk factor of grade III-IV bone marrow suppression (χ2=16.975, P=0.001). No significant differences in the counts of white blood cell, hemoglobin and platelet were observed before chemotherapy at relapse between patients with and without prior radiotherapy. Reduction of white blood cell counts, absolute value of neutrophil cell and platelet counts composited majority type of grade III and IV bone marrow suppression. Conclusions: The prior pelvic radiotherapy significantly increased the incidence of bone marrow suppression during chemotherapy in recurrent cervical cancer patients. When treating recurrent cervical cancer patients with chemotherapy who had prior radiotherapy, especially for those experienced external beam radiation therapy, essential attention and timely intervention are recommended to ensure completion of chemotherapy and clinical efficacy.

Human papillomavirus maybe is a critical player in the regulation of chemoresistance related factors (P53, Rb, TWIST, Bcl-2, Bcl-XL, c-IAP2, cytochrome C, and caspase 3) in breast cancer

As one of the frequent malignancies, breast cancer (BCa) is the foremost reason for cancer-related deaths among women. The role of Human papillomavirus (HPV) in chemoresistance has rarely been investigated in previous studies. The current study sets out to the possible role of HPV in BCa chemoresistance. In this research, 90 BCa tissue and 33 normal breast tissue were collected. We evaluated the presence of the HPV genome along with the viral (E2, E6, E7) and cellular gene expression associated with cell resistance to death. Statically significant differences in the prevalence of HPV between the BCa group (25.2% or 23/90) and the control group (21.8% or 7/32) were not found. HPV-16 and HPV-18 genotypes were the abundant HPV genotypes. Resistance to the Adriamycin-Cyclophosphamide (AC), paclitaxel regimen was elevated in the HPV- group (56/70) in comparison to the HPV+ group (14/70). Nevertheless, there was no significant difference in the prevalence of resistance to AC + paclitaxel + triple-negative breast cancer combination therapy between the HPV+ group (9/20) and in the HPV- group (11/20). In the BCa group in contrast to the control group, the expression level of Bcl-2, BCL-XL, and c-IAP2 demonstrated a significant decrease, while, the expression level of cytochrome C and caspase 3 was significantly increased. This study suggests that HPV infection might contribute to BCa chemoresistance through disrupt cellular genes involved in cell death.

P-426 In vitro and in vivo toxicity of carboplatin and paclitaxel regimen on BRCA-mutated ovarian tissue fragments

Abstract Study question Does carboplatin and paclitaxel regimen have a toxic cumulative impact on the ovarian reserve of young breast cancer patients with germline Breast Cancer (BRCA) mutation? Summary answer Based on follicle classification and survival through apoptosis and DNA repair mechanism recruitment analyses, gonadotoxic but no cumulative effect was observed in BRCA-mutated ovarian tissue. What is known already Ovarian function recovery and fertility issues remain major concerns for young patients diagnosed with cancer. Breast cancer is the first cancer diagnosed among women under 40 years and around 10% of them are BRCA germline mutation carriers. Beside their predisposition to breast and ovarian cancers, BRCA carriers might be more sensitive to chemotherapy-induced gonadotoxicity due to the role of BRCA in DNA repair mechanism. Current therapies for BRCA-mutated breast cancer patients often include carboplatin and paclitaxel, drugs that are both considered as moderately gonadotoxic. However, the effect of combined therapy in BRCA-mutated ovarian tissue is unknown. Study design, size, duration Ovarian tissue cryopreserved for fertility preservation before chemotherapy and donated for research by breast cancer patients with or without BRCA1/2 mutation (&amp;lt; 35 years at diagnosis) were used in this study. Two models were investigated: 3 days in vitro culture with carboplatin (10 µg/mL) and/or paclitaxel (1 µM) and ovarian tissue xenograft into mice followed by 3 weeks injections of carboplatin (50mg/kg/week) and paclitaxel (10mg/kg every 3 days). Control conditions were performed for each model. Participants/materials, setting, methods Ovarian tissue from 3 BRCA-mutated and 3 non-mutated patients were thawed and exposed in vitro and in vivo to chemotherapy. Follicle density (number of follicles/mm²) as well as ratios of quiescent/activated and healthy/atretic follicles were evaluated following haematoxylin-eosin staining. Apoptosis and DNA repair mechanisms were analysed using TUNEL/GDF9 co-staining and phosphorylated H2A histone family member X (γH2AX)/ZP-3 co-staining, respectively. Genes expression level will be evaluated on isolated follicles to assess the activation process. Main results and the role of chance First, the impact of in vitro culture and in vivo xenotransplantation was evaluated by follicle counting and classification. A decrease of follicular density (5 to 95% irrespective of patient, model, nor condition) and an increase of activated and atretic follicles was observed after both in vitro and in vivo experiments in all conditions. However, a slight increase of quiescent follicle pool was observed in the in vitro control condition, with no difference between mutated and non-mutated fragments. Then, immunofluorescence staining was performed to evaluate follicle damage. For quantification, 30 to 150 follicles per patient were counted within each condition and classified as positive if at least one cell was stained. Apoptosis was assessed with TUNEL/GDF9 co-staining. In both models, the ratio of positive follicles was higher in fragments treated with chemotherapy (40-60%) compared to control conditions (15-20%). Recruitment of DNA repair complex was analysed using γH2AX/ZP3 co-staining. In both models, an increase in positive follicles ratio was observed in treated fragments (15-40%) compared to control conditions (5-10%). Interestingly, the positive follicles ratio was lower in BRCA-mutated (15-18%) than in non-mutated fragments (25-40%) after 3-days in vitro culture, irrespective of the treatment used. Limitations, reasons for caution Reasons of caution include the high inter-variations between patients as well as intra-variations in one patient regarding follicular density within ovarian tissue. Moreover, BRCA-mutated patients included (27.67 ± 2.08) are younger than control ones (33.67 ± 1.53). Ongoing experiments with additional patients should support the results already obtained. Wider implications of the findings Carboplatin and paclitaxel combined exposure in vitro or in vivo does not seem to have a cumulative deleterious impact on ovarian reserve. Ovarian tissue with BRCA-mutation did not appear to be more sensitive to chemotherapy exposure. Further investigations focusing on DNA repair mechanisms will be performed in both models. Trial registration number Not applicable