Administration Of Postoperative Chemotherapy Research Articles

A Gallium-doped cement for the treatment of bone cancers. The effect of ZnO ↔ Ga2O3 substitution of an ionomeric glass series on the rheological, mechanical, pH and ion-eluting properties of their corresponding glass polyalkenoate cements

The primary treatment for patients suffering from bone cancers is resection of the tumour followed by reconstruction of the damaged bone. Despite the administration of post-operative chemotherapy, tumour recurrence continues to present itself as a severe complication leading to re-operation. Attempts to incorporate chemotherapeutic drugs into bone cements elicits local toxic effects on healthy bone, which could compromise implant fixation. Alternatively, the local administration of gallium (Ga) may prove to be more effective. This report considers the development of a Ga ionomeric glass series (0.48SiO2-0.355ZnO-0.06CaO-0.08SrO-0.02P2O5-0.005Ta2O5, with 0.01–0.05 mol% substitution for ZnO). X-ray Diffraction (XRD) confirmed the amorphous glass structure and Energy Dispersive x-ray Fluorescence (EDXRF) verified the successful addition of Ga into the glass series at the expense of Zinc (Zn). A Ga-GPC series was then formulated by mixing the glass particles with aqueous poly(acrylic) acid (PAA) and trisodium citrate (TSC). Fourier transform infrared (FTIR) spectroscopy demonstrated no structural changes to the GPC matrix with the incorporation of Ga. Measurements of the rheological properties demonstrated an exponential increase in setting time with increasing Ga content. Furthermore, the addition of 3 mol% Ga demonstrated deleterious effects on the GPC’s mechanical properties and an analysis of pH confirmed that it decreased with increasing Ga content, suggesting a reduction in glass reactivity and PAA cross-linking. Finally, inductively coupled plasma—optical emission spectrometry (ICP-OES) demonstrated the controlled release of Ga across the GPC series, which will prove beneficial to future in vitro studies.

Abstract PS12-03: Letrozole and palbociclib versus 3rd generation chemotherapy as neoadjuvant treatment in luminal breast cancer: Survival results of the UNICANCER-NeoPAL study

Abstract Background Palbociclib is a CDK4/6 inhibitor with demonstrated survival benefits in combination with endocrine therapy in advanced luminal breast cancer (LBC). Its potential role in early breast cancer is currently explored. The NeoPAL trial compared letrozole-palbociclib (LETPAL) combination to standard chemotherapy (CT) as neoadjuvant treatment in patients with high-risk LBC. Both LETPAL and CT were associated with poor pathological response, and equivalent clinical responses, while LETPAL let to encouraging biomarker responses in Prosigna®-defined high-risk LBC. We now evaluate the survival outcomes of both groups. Patients and Methods NeoPAL (UCBG10/4, NCT02400567) is a randomized, parallel, non-comparative phase II study. Postmenopausal women with ER-positive, HER2-negative, Prosigna®-defined luminal B, or luminal A and node-positive, stage II-III breast cancer, not candidate for breast-conserving surgery, were randomly assigned to either letrozole (2.5 mg daily) and palbociclib (125 mg daily, 3 weeks/4) during 19 weeks (LETPAL), or to FEC100 (5FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) x3 21-day courses followed by docetaxel 100 mg/m2 x3 21-day courses (CT). Secondary endpoints included progression-free survival (PFS) and invasive-disease free survival (iDFS), all measured from the date of randomization. Exploratory objectives aimed at evaluating the impact of PEPI score and residual cancer burden (RCB) on survival outcomes in both arms. Results 53 pts were randomized in each arm (both with 11% Luminal A N+ and 89% Luminal B). 23 of the 53 pts in the LETPAL arm received postoperative adjuvant chemotherapy. Median follow-up is 40.4 months [0-56.6]. 11 progressions have been observed (10 metastatic events, 1 regional progression), of which 3 were in the LETPAL and 8 in the control arm. Two additional iDFS events were observed in the LETPAL arm (secondary malignancies). PFS (HR = 1.01; 95%CI [0.36; 2.90], p=0.98) and iDFS (HR= 0.83; 95%CI [0.31; 2.23], p=0.71) did not differ between both arms. 40 months PFS rate is 86.7% (78.0-96.4) and 87.2% (78.1-97.4) in LETPAL and CT arms respectively. PEPI (PEPI II/II vs I: HR 0.80, 95%CI 0.18-3.67) and RCB scores (RCB II/III vs 0/I: HR 1.36; 95%CI 0.17-10.6) did not appear as independent predictors of PFS or iDFS. Conclusions Despite its small size, NeoPAL suggests that a neoadjuvant LETPAL strategy, together with selected postoperative administration of chemotherapy, may spare chemotherapy in some pts with luminal breast cancer while allowing very good long-term outcomes. Citation Format: Suzette Delaloge, Sylvain Dureau, Véronique D'Hondt, Isabelle Desmoulins, Pierre-Etienne Heudel, François Duhoux, Christelle Levy, Florence Lerebours, Marie Ange Mouret-Reynier, Florence Dalenc, Jean-Sébastien Frenel, Christelle Jouannaud, Laurence Venat-Bouvet, Suzanne Nguyen, Cécile Callens, David Gentien, Jerome Lemonnier, Anne Vincent-Salomon, Hélène Manduzio, Paul-Henri Cottu. Letrozole and palbociclib versus 3rd generation chemotherapy as neoadjuvant treatment in luminal breast cancer: Survival results of the UNICANCER-NeoPAL study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-03.

Simultaneous versus staged resection of rectal cancer and synchronous liver metastases (RESECT)

Staged resection is preferred to treat synchronous rectal cancer with liver metastases. Simultaneous resection of rectal cancer with synchronous liver metastases may potentially decrease postoperative complications, thereby improving quality of life, decreasing health care costs, and avoiding delays in postoperative chemotherapy administration. We evaluated the safety of simultaneous resection. We searched Medline, Embase, and PubMed for studies comparing simultaneous versus staged resection. Study selection, data abstraction, risk of bias (ROB), and quality of the evidence (QOE) assessment were performed in duplicate. The primary outcome was overall postoperative complications. The secondary outcome was postoperative complications in the intervention group. ROB and QOE were assessed using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). 4456 abstracts were retrieved; 18 retrospective cohort studies reported postoperative complications in the intervention arm, with six comparing intervention (288 patients) to control (287 patients). The odds ratio (OR) for overall complications was 0.93, 95% confidence interval (CI): 0.64–1.35, and for major complications was 0.77, 95%CI: 0.40–1.50. Proportion of complications (intervention arm): 41%, 95%CI: 33–50%. ROB was moderate. Simultaneous resection of synchronous rectal cancer with liver metastases carries a similar risk of overall and major complications compared to the staged approach. However, QOE is very low and a simultaneous approach ought to be pursued only in selected patients until better evidence is available.

Prognostic factors in patients who received surgery for colorectal cancer with peritoneal metastasis.

574 Background: Peritoneal metastasis (PM) in patients diagnosed with colon cancer is associated with a poor prognosis. We aimed to analyze prognostic factors associated with PM in patients diagnosed with colorectal cancer (CRC). Methods: We evaluated 237 patients who underwent surgery between 2002 and 2016 for CRC with PM. The extent of PM was evaluated using the Peritoneal Cancer Index (PCI). Clinicopathological variables, PCI score, surgical curability, and the administration of postoperative chemotherapy were evaluated. Overall survival was analyzed using the Kaplan-Meier method. Multivariate analysis was performed to assess the prognostic value of these variables, using the Cox regression model. Results: Our patients included 119 men and 118 women with a median age of 64 (range: 21–90) years. The primary tumor sites were the right-sided colon (n = 103), left-sided colon (n = 84), and rectum (n = 50). The median PCI score was 4 (range: 1–30). Synchronous PM was detected at the time of diagnosis of the primary tumor in 165 patients (69.6%). Distant metastases except peritoneal metastases was detected in 137 patients (57.8%). R0 resection was performed in 62 patients (19.0%). Postoperative chemotherapy was performed in 165 patients (69.6%). The median survival time in all patients was 19.4 (range: 0–30) months, and the five-year overall survival rate was 16.3%. Multivariate analysis revealed that PCI ≤ 5 (hazard ratio [HR]: 2.56, 95% confidence interval [CI]: 1.56-4.32, P < 0.01); the absence of distant metastasis, except peritoneal metastasis (HR: 1.65, CI: 1.15-2.40, P < 0.01); R0 resection (HR: 4.21, CI: 2.44-7.50, P < 0.01) affected the survival rate. Conclusions: Our results show that a low PCI, the absence of distant metastasis except peritoneal metastasis, and R0 resection are prognostic factors in patients diagnosed with PM-CRC.

Multigene Signature Panels and Breast Cancer Therapy: Patterns of Use and Impact on Clinical Decision Making

A growing body of evidence supports the use of multigene signature panels (MSPs) in predicting recurrence risk in patients with invasive breast cancer. This study aimed to evaluate trends in MSP use over time and the effect of MSPs on administration of postoperative chemotherapy. The National Cancer Database was queried for all women with invasive breast cancer who underwent resection between 2011 and 2014 and had information about performance of an MSP, hormone receptor status, and receipt of chemotherapy. Multigene signature panel use over time was evaluated, and patterns of use of Oncotype DX (ODX) and MammaPrint (MP) were compared. In a total of 476,128 patients, an MSP was obtained in 153,782 (30.2%). Multigene signature panel use increased over time and was associated with a decreased rate of chemotherapy administration (24.6% MSP vs 37.2% no MSP; p < 0.001). Oncotype DX remained the most common MSP used throughout the study period. Oncotype DX was used more commonly in stage I disease than MP, and MP was used more commonly in stage II and III disease. MammaPrint was more commonly used in hormone receptor-negative patients, human epidermal growth factor receptor 2-positive patients, and patients with positive lymph nodes. Postoperative chemotherapy was administered to a higher proportion of patients assessed with MP than with ODX (41.3% vs 23.4%, respectively; p < 0.001). Use of MSPs among patients with breast cancer has increased over time and is associated with a decreased use of adjuvant chemotherapy. Oncotype DX continues to be the most widely used MSP, although MP use has increased over time. Future studies are warranted to determine the optimal use of these MSPs in risk assessment and postoperative decision making.

Prognostic factors influencing survival in small bowel neuroendocrine tumors with liver metastasis.

e15688 Background: Management of liver metastasis in patients with small bowel neuroendocrine tumors (SBNET) remains unclear. Complete surgical resection improves long term survival however factors that influence overall prognosis are not clear. Methods: Database review identified 301 patients diagnosed with SBNET from 1990 to 2013. Only patients with known liver metastasis who underwent resection of the primary tumor were included. Outcomes among patients who underwent complete surgical resection, incomplete debulking of liver metastasis, and resection of the primary tumor alone were compared. The Kaplan-Meier method was used for survival estimates and Cox regression was used to identify predictors of death. Results: 111 patients met study criteria. Median age was 59 years (range 16-80); 49% were male. The terminal ileum (47/111, 42%) was the most common primary tumor location. The median number of liver lesions was 8.5 (range 1-31) and median lesions resected was 1 (range 0-31). In addition to resection of the primary tumor, 36 patients (32%) had no liver resection (NR), 41 (36.9%) had complete resection of liver disease (R0) and 34 (30%) had incomplete resection of liver metastasis (R1). 58 patients (36%) had one or more wedge resections, 12 (10.8%) underwent segmentectomy and 5 (4.5%) had a lobectomy. 33 (29.7%) patients underwent post-operative chemoembolization, 25 (22.5%) had radioembolization and 23 (20.7%) had radiofrequency ablation. The R1 group differed from the R0 group in median size of primary tumor (2.5 cm R1 vs 1.6 cm R0, p = 0.05) and median number of positive lymph nodes (5.0 R1 vs 3.0 R0, p = 0.05). The 5-year OS was 80.9%, 81.1% and 100% for NR, R1 and R0 groups respectively (p = 0.01). 10-year OS did not differ between groups (72.8% NR vs 81.1% R1vs 82.5% NR, p = 0.31). Cox regression showed post-operative administration of chemotherapy (HR = 3.68, p &lt; 0.01) and higher tumor grade (HR = 18.4, p = 0.02) increased risk of death. Conclusions: In patients with SBNET with liver metastasis, higher tumor grade and post-operative chemotherapy increased risk of death. However, resection of the primary tumor along with liver metastasis improves the 5-year OS with complete cytoreduction providing the most benefit.

Perioperative platin-based chemotherapy for locally advanced esophagogastric adenocarcinoma: Postoperative chemotherapy has a substantial impact on outcome

BackgroundA combination of platin-based perioperative chemotherapy (PBPC) plus surgical resection has become the standard of care in Europe for locally advanced esophagogastric adenocarcinoma (EGAC). In contrast to preoperative chemotherapy, the postoperative administration of chemotherapy is omitted in a high percentage of patients. We conducted this database study to analyse the impact of postoperative completion of perioperative chemotherapy on patient outcome. MethodsPatients with EGAC (cT3-4 and/or cN+) were treated with preoperative PBPC plus curative surgical resection. Patient demographics, postoperative tumour stages, histopathological regression (HPR) and administration of postoperative chemotherapy were correlated with overall survival. ResultsOf one-hundred-thirty-four patients, 76 received preoperative docetaxel, folinic acid, fluorouracil, oxaliplatin (FLOT), 53 patients epirubicin, cisplatin, folinic acid (ECF) and 5 epirubicin, oxaliplatin, capecitabine (EOX) chemotherapy. The 5-year-survival for the whole collective was 58%. Designated postoperative chemotherapy was omitted in 36% of the patients. 5-year-survival was 75.8% in patients who received pre- and post-operative chemotherapy and 40.3% in patients with only preoperative chemotherapy (p < 0.001). Histopathological regression, postoperative nodal status and administration of postoperative chemotherapy were identified as independent prognostic factors. Analysis of subgroups revealed a pronounced survival benefit after administration of postoperative chemotherapy in patients with ypN+ stages (5-year-survival 64.5% vs 9.7%, p = 0.002) and poor HPR (5-year-survival 55.5% vs 19.3%, p = 0.015). ConclusionOur study provides further evidence that administration of postoperative chemotherapy may contribute to the achieved survival benefit of PBPC in patients with EGAC and implies a beneficial effect especially in presence of lymphonodular tumour involvement and limited HPR.

Predicting early intrahepatic recurrence after curative resection of colorectal liver metastases with molecular markers.

The aim of this case-control study was to identify clinicopathological factors and test three relevant biomarkers for their ability to predict early intrahepatic recurrence after curative liver resection for colorectal liver metastases (CLM). Of the 184 patients with CLM undergoing hepatectomy between January 2007 and December 2009, thirty patients had intrahepatic disease recurrence within 6 months. The control group was randomly selected from a cohort of patients between April 1997 and December 2005 who have survived without disease recurrence after CLM resection for over 5 years. Both groups were matched for size of metastasis greater than 5.0 cm, the presence of multiple metastases, and synchronous versus metachronous CLM. The final study population consisted of 60 patients with CLM undergoing R0 hepatectomy, 30 of whom had early intrahepatic-only recurrences (study group) and 30 patients without recurrence for more than 5 years (control group). Both groups were analyzed and compared for the presence of clinical factors and expression levels of CD133, survivin, and Bcl-2 within tumor tissue. Characteristics of patients were similar between the two groups except primary tumor location and administration of postoperative chemotherapy. Expression level of CD133 and survivin were significantly increased in tumors of patients with recurrence compared to patients without recurrence. On multivariate analysis high tumor expression levels of CD133 (odds ratio [OR] 14.7, confidence interval [CI] 1.8-121.3, p = 0.012) and survivin (OR 9.5, CI 2.1-44.3, p = 0.004) and postoperative chemotherapy (OR 4.8, CI 1.01-22.9, p = 0.049) were independent factors associated with early intrahepatic recurrence. Tumor expression levels of CD133 and survivin may be a useful predictor of early intrahepatic recurrence after hepatectomy for CLM. Administration of postoperative chemotherapy may prevent early intrahepatic recurrence.

Prognostic factors after R2 surgery in patients with advanced gastric cancer.

140 Background: In patients with advanced gastric cancer, chemotherapy is a standard treatment if they have non-curable factors. However, gastrectomy is sometimes performed even in patients having non-curable factors, particularly when they have tumor associated symptoms. The aim of this study is to investigate clinicopathological characteristics of patients who underwent R2 surgery, and to identify prognostic factors. Methods: This study included 157 patients who underwent gastrectomy with macroscopic residual disease (R2 surgery) between September 2002 and June 2011 at the Shizuoka Cancer Center. Clinicopathological characteristics and surgical outcomes were investigated. In addition, we conducted Cox-proportional Hazards model which included age, sex, number of non-curable factors, chemotherapy, macroscopic type, histology, and postoperative intraabdominal infectious complications as covariates, to identify independent prognostic factors after R2 surgery. Results: There were 103 male and 54 female patients with median age of 69 years. The reasons why R2 surgery was performed were low oral intake due to stenosis in 120 patients and bleeding in 54 patients. Total gastrectmy was the most frequently performed procedure (93 patients) followed by distal gastrectomy (61 patients) Median operation time and intraoperative blood loss were 193 minutes and 337 mg, respectively, and intraabdominal infectious complications (Clavien-Dindo classification grade II or more severe) were observed in 24 patients (15.3%). Chemotherapy was given after surgery in 112 patients (71.3%) with median survival time of all patients being 8.7 months. Multivariate analysis identified postoperative chemotherapy (Hazard ratio, 0.34; 95% confidential interval, 0.24 – 0.65) and postoperative intraabdominal infectious complications (Hazard ratio, 1.74; 95% confidential interval, 1.06 – 2.88) as independent prognostic factors. Conclusions: The incidence of postoperative infectious complications after R2 surgery was thought to be higher than that after curative gastrectomy reported before. Safe procedure and administration of postoperative chemotherapy would be necessary to offer improved overall survival after R2 surgery.

The Risk of Umbilical Hernia and Other Complications with Laparoendoscopic Single-Site Surgery

Study Objective To estimate the risk of umbilical hernia and other latent complications in women who underwent laparoendoscopic single-site surgery (LESS) for a gynecologic indication. Design Retrospective, nonrandomized clinical study (Canadian Task Force classification II-2). Setting Four tertiary care academic medical centers. Patients Women undergoing LESS for a benign or malignant gynecologic indication from 2009 to 2011. Interventions A total of 211 women underwent LESS via a single 1.5- to 2.0-cm umbilical incision. All surgeries were performed by advanced gynecologic laparoscopists. Incisions were repaired with a running, delayed absorbable suture. Subject demographics and clinical variables were collected and surgical outcomes analyzed. Measurements and Main Results Median age and body mass index were 45 years and 30 kg/m 2, respectively. Approximately half of study subjects underwent a hysterectomy with or without salpingo-oophorectomy, and 15% had a diagnosis of cancer. Overall, 0.9% of women were diagnosed with a preoperative umbilical hernia, and 2.4% of women experienced a major perioperative complication. After a median postoperative follow-up time of 16 months, 2.4% had development of an umbilical hernia. However, 4/5 of these women had significant risk factors for fascial weakening independent of LESS, including requirement for a second abdominal surgery in 1 subject and a cancer diagnosis with postoperative chemotherapy administration in 2 subjects. When these subjects deemed “high risk” for incisional disruption were excluded from the analysis, the umbilical hernia rate was 0.5% (1/207). On univariable analysis, obesity was the only factor associated with complications (p = .04). Conclusion When performed by advanced laparoscopic surgeons, laparoendoscopic single-site gynecologic surgery is associated with a low risk of major adverse events. Additionally, the overall umbilical hernia rate was 2.4% and was lower (0.5%) in subjects without significant comorbidities.

Benzalkonium bromide as a new potential instillation drug for bladder cancer: Hypothesis and pilot study

SummaryNon-muscle-invasive urothelial carcinoma of the bladder has a high rate of recurrence, necessitating use of a variety of adjuvant treatments. A single, immediate post-operative administration of chemotherapy is an important measure for reducing the rate of recurrences, but the overall effect is not satisfactory and the treatment is a burden to the patient. Hence, there is a need for a new, more effective and cheaper agent for adjuvant treatment of non-muscle-invasive bladder carcinomas.Although cationic surfactants such as benzalkonium salts are used clinically and hygienically for the control of bacterial growth, there have been reports that cationic surfactants such as benzethonium chloride induce apoptosis in normal and in cancerous cells. We report our experience with benzalkonium bromide (BB) accidentally administered into a patient‘s bladder as saline. It caused severe hematuria and pain, but after a week of persistent administration in the bladder, the patient was cured, as supported by evidence from cystoscopy, indicating that BB destroys bladder mucosa and suggesting that BB maybe a novel agent for use in a single, immediate post-operative administration. We present preliminary data to support this hypothesis and provide discussion we hope will be useful as the foundation for further experiments.

Adjuvant chemotherapy for bladder cancer

Radical cystectomy is a standard treatment for patients with muscle-invasive bladder cancer. The presence of occult micrometastatic disease is responsible for both local and distant failure after radical surgery. Postoperative administration of chemotherapy in bladder cancer patients can theoretically give the same survival advantage demonstrated in patients with breast and colon cancer. Studies evaluating adjuvant chemotherapy in patients with pT3–pT4 and/or pN+ M0 disease have major deficiencies in terms of sample sizes, early stopping of patient entry, statistical analyses, reporting of results and drawing conclusions. A recent meta-analysis including all previously published randomized trials concludes that, currently, there is insufficient evidence to reliably recommend adjuvant chemotherapy. The results of appropriately sized randomized trials are needed before any definitive conclusions can be drawn.

Carcinoma corticosuprarrenal con afectación de aurícula derecha. cirugía mediante by-pass cardiopulmonar

IntroductionPrimary adrenal carcinoma is a low incidence tumour. About 50% are functional and the majority result in Cushing's syndrome, while detection of the rest is commonly incidental. Surgical management is through radical surgery. Case reportA 36-year old female who presented with a one-month old abdominal pain in the hypochondrium and the right lumbar fossa. Physical examination found a discretely painful mobile mass. Adrenal hormones values were normal. Ultrasound and CT studies detected a 14-cm adrenal tumour with cava vein thrombosis up to the right auricle. The surgical procedure included laparotomy, liver mobilisation and cardiopulmonary by-pass. The thrombus was completely removed by auriculotomy. Therapy with mitotane and 5-fluorouracil was then instituted. Thirteen months after surgery the patient is asymptomatic and tumour free. RemarksDissemination of adrenal tumours to veins ranges between 6 to 30%. Clinical manifestation of cava vein and auricle involvement is variable but it may develop with no symptoms due to collateral circulation. Pre-operative diagnosis is critical to plan for adequate surgical approach. Ultrasound and computerised tomography can adequately diagnose the process, but nuclear magnetic resonance provides more information on the thrombus extension and location. In the absence of node spread, local extension, or invasion of the cava wall prognosis is similar to that of patients with no vein involvement. The best therapeutic option is surgery with removal of the lesion and cardiopulmonary by-pass. Survival at 5 years is 43%. Post-operative administration of chemotherapy with mitotane is a useful and recommendable choice.

Reinnervated Free Muscle Transplantation for Extremity Reconstruction

Reinnervated free muscle transplantation was used to rehabilitate severely impaired extremities in patients with brachial plexus palsy and for functional limb salvage in cases of traumatic muscle loss or radical excision of a malignant soft-tissue tumor. Fifty-eight reinnervated free muscle transplantations were implanted in 46 patients. Twenty-four patients had simultaneous reconstruction of two functions, such as finger and elbow flexion lost to brachial plexus palsy; 12 patients underwent double muscle transplantation; 15 patients received free muscle transplants for limb salvage after tumor excision in an extremity; 6 transplants replaced traumatic muscle loss; and 1 was used for reconstruction of finger flexion after poliomyelitis. Twenty-six latissimus dorsi, 25 gracilis, and 7 rectus femoris muscles were used as donors. All muscles survived. The postoperative follow-up ranged from 18 months to 4 years. The speed and extent of reinnervation of the transplanted muscle depended on the choice of recipient nerve, the patient's age, and the occurrence of postoperative vascular complications. Neurotization by the spinal accessory nerve or the posterior interosseous nerve resulted in the most rapid recovery. The administration of postoperative chemotherapy did not delay recovery of function. Free muscle transplantation is consistently successful and provides a functional extremity in severely handicapped patients.