Pre-chemotherapy Value Research Articles

Clinical Characteristics and Treatment Outcomes of Patients with Ovarian Germ Cell Tumor Treated at a Tertiary Care Center in Patna, India

Ovarian germ cell tumors are rare tumors, mainly diagnosed in young females with a good prognosis if presented earlier. The objective of this study was to evaluate the clinicopathological features, treatment and outcome of the malignant ovarian germ cell tumors. We retrospectively reviewed 37 patients of malignant ovarian germ cell tumors registered at the Department of Radiation Oncology All India Institute of Medical Sciences (AIIMS), Patna, from August 2014 to September 2019, and analyzed their demographic profile, treatment, outcome and survival. The median age at presentation was 15 years with a median duration of symptoms of 18 weeks. Abdominal pain and abdominal pain with lump were the main presenting symptoms of 45.9% and 45.9%, respectively. The median pre-chemotherapy value of AFP was 286 ng/ml, βHCG was 8.2 mIU/ml, and LDH was 470 U/L. Fertility-preserving surgery was done in 64.9% of cases. 35.1%, 21.6%, 29.7% and 13.5% cases were in stage I, stage II, stage III and stage IV, respectively. Adjuvant systemic chemotherapy was indicated in 94.6%, and chemotherapy was not indicated in 5.4% of patients. Non-dysgerminoma was the most common histopathological type (67.7%) followed by mixed germ cell tumors and dysgerminoma in 18.9% and 13.5%, respectively. The mean follow-up duration was 40 months, 32.4% of patients developed recurrence, and mean time to recurrence was 25 months. Malignant ovarian germ cell tumor is a treatable disease, and selected patients may be managed with fertility-preserving surgery. It was observed in this study that malignant ovarian germ cell tumors have a good prognosis.

Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: A protocol for a randomized phase 2 trial

Although cisplatin is one of the most effective agents against various pediatric cancers, it is sometimes difficult to manage due to its dose-limiting nephrotoxicity. Magnesium sulfate (Mg) showed a kidney-protective effect against cisplatin-induced nephrotoxicity (CIN) by regulating renal platinum accumulation both in vitro and in vivo, and the body of clinical data demonstrating the efficacy of this drug in adult cancer patients is increasing.In this open, multicenter, phase-2, randomized trial, patients under age 18 years who are scheduled to receive cisplatin-containing chemotherapy will be enrolled and randomly allocated either to an Mg supplementation arm in even-numbered chemotherapy courses (arm AB) or to another arm in odd-numbered courses (arm BA), with a 1:1 allocation. Analysis objects will be reconstructed into two groups depending on whether the chemotherapy course has Mg supplementation (group B) or not (group A). The primary endpoint is the proportion of chemotherapy courses resulting in elevated serum creatinine equal to or greater than 50% of the prechemotherapy value. For the secondary endpoints, various parameters for measuring kidney function, such as serum cystatin-C, B2M, L-FABP, NGAL, and urinary NAG in the two groups will be compared. A sample size based on alpha = 5% and 80% power requires at least 40 samples per group (ideally, 60 samples per group).If Mg demonstrates efficacy, a phase-3 study to confirm the prophylactic effect of Mg supplementation in both acute and chronic CIN will be developed using novel and better biomarkers. Trial registrationUMIN-CTR (http://www.umin.ac.jp/icdr/index.html) Identifier UMIN000029215.

SERUM VALUES OF ALKALINE PHOSPHATASE AND LACTATE DEHYDROGENASE IN EWING'S SARCOMA.

ABSTRACTObjective: To study the relationship between the serum levels of alkaline phosphatase (AP) and lactate dehydrogenase (LDH), and the percentage of tumor necrosis (TN) in patients with Ewing´s Sarcoma (ES). Methods: This is a case series with retrospective evaluation of patients with diagnosis of ES divided into 2 groups: Group 1, patients whose serum levels of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were obtained in the staging phase before preoperative chemotherapy (CT), and Group 2, patients whose values were measured after completion of the preoperative CT. The percentage of tumor necrosis (TN) of surgical specimens extracted in surgery was also evaluated. Results:Eighty four medical records from 1995 to 2015 were included. Both AP as LDH decreased in the patients studied, the pre CT value being higher than the post CT value. The average decrease of LHD was 272.95 U/L and AP was 10.17 U/L. The average tumor necrosis was 65.12 %. There was no statistical correlation between serums levels and the tumor necrosis percentage. Conclusion: The serum levels values of AP and LDH are not predictors for chemotherapy-induced necrosis in patients with ES. Level of Evidence IV, Case Series.

Absence of effect ofSLC22A2genotype on cisplatin-induced nephrotoxicity in oesophageal cancer patients receiving cisplatin and 5-fluorouracil: report of results discordant with those of earlier studies

Cancer patients treated with cisplatin chemotherapy frequently experience drug-induced nephrotoxicity. Clinical studies using a single chemotherapeutic regimen or large sample sizes for patients with the SLC22A2 808T allele have not been reported. Here, we examined 95 patients with oesophageal cancer who received 5-fluorouracil and cisplatin (FP) to determine whether nephrotoxicity was affected by SLC22A2 808G>T polymorphism. The change rate of the estimated glomerular filtration rate (eGFR) was used for the evaluation of cisplatin-induced nephrotoxicity and calculated for each patient according to the following formula: change rate = (prechemotherapy value - post-chemotherapy value)/prechemotherapy value. Genotyping of SLC22A2 808G>T was carried out using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The eGFR after FP chemotherapy was significantly lower than that before chemotherapy, and the mean difference in eGFR was 25·7 mL/min (P < 0·01). There was no significant difference in the mean change rate of the eGFR following FP chemotherapy between the SLC22A2 808GG genotype (n = 70) and the 808GT+TT genotypes (n = 25) (27·9% and 27·8%, respectively). In multiple regression analyses, the change rate of eGFR following FP chemotherapy was associated with the eGFR value prior to chemotherapy (P = 0·04). In FP chemotherapy for oesophageal cancers, cisplatin-induced nephrotoxicity seems to be unaffected by the SLC22A2 808G>T polymorphism. The eGFR prior to chemotherapy might be an important risk factor for cisplatin-induced nephrotoxicity. Our present study was estimated with a single chemotherapeutic regimen, eGFR, and was calculated using serum creatinine, age and the sex of the patient and sample sizes of 25 patients with SLC22A2 808T allele. However, further examinations with a larger sample size to corroborate the study results might be necessary.

Use of 99mTc-MIBI scintigraphy in the evaluation of the response to chemotherapy for osteosarcoma: comparison with 201Tl scintigraphy and angiography

In the treatment of osteosarcoma, the chemotherapeutic effect influences decisions regarding the surgical margin, continuation of chemotherapy, and choice of anticancer drugs for further chemotherapy. Therefore, it is necessary to evaluate the response to chemotherapy in the middle of the chemotherapy course. In this study, we investigated the use of (99m)Tc-hexakis-2-methoxyisobutyl-isonitrile ((99m)Tc-MIBI) scintigraphy in evaluating the response to chemotherapy of patients with osteosarcoma in comparison with (201)Tl scintigraphy and angiography. A total 45 patients with osteosarcoma were examined using (99m)Tc-MIBI scintigraphy, (201)Tl scintigraphy, and angiography to evaluate their response to chemotherapy. The percentage reduction in the uptake ratios (ΔUR) calculated as 100×[(prechemotherapy value-postchemotherapy value)/prechemotherapy value] were compared with histological assessments. Similarly, changes in tumor vascularity assessed by angiograms were compared with histological assessments. On the angiographic findings, the results were classified as complete response (CR), partial response (PR), no change (NC), or progressive disease (PD). On the images, ΔUR in (99m)Tc-MIBI≥30% and ΔUR in (201)Tl≥30% were classified as responder, as were CR and PR in angiograms. The therapeutic effect was assessed by histopathological examination of the resected specimens. The tumors of poor responders showed less than 90% necrosis, whereas the tumors of good responders showed 90% or more necrosis. Sensitivity, specificity, and accuracy were 73.9, 84.2, and 78.6%, respectively, for (99m)Tc-MIBI (κ=0.57); 80.0, 61.1, and 72.1%, respectively, for (201)Tl (κ=0.42); and 91.7, 35.0, and 65.9%, respectively for angiography (κ=0.28). (99m)Tc-MIBI could be effectively used to predict the final response to chemotherapy of osteosarcoma.

Prediction of final tumor response to preoperative chemotherapy by Tc‐99m MIBI imaging at the middle of chemotherapy in malignant bone and soft tissue tumors: Comparison with Tl‐201 imaging

The aim of this study was to assess the predictive power of 99mTc-MIBI scintigraphy performed in the middle of chemotherapy, for the final tumor response to chemotherapy, and compare it to that of (201)Tl in malignant bone and soft tissue tumors (MBST). Sixty-eight patients with MBST underwent 99mTc-MIBI and 201Tl scintigraphies at 15 min after tracer injection before the first, and after the third, chemotherapy cycles. After five cycles of chemotherapy and tumor resection, therapeutic effect was assessed by histopathology. Less than 90% and > or =90% necrosis were judged as poor and good response to chemotherapy, respectively. Tracers uptake ratios were calculated by dividing the lesion count density by that of the background. 99mTc-MIBI perfusion index was also calculated. The % reduction of the perfusion index (DeltaPI) and uptake ratios (DeltaUR) calculated by 100 x [(prechemotherapy value--postchemotherapy value)/prechemotherapy value] were compared with histologic response. The sensitivity, specificity, and accuracy for the prediction of effective chemotherapy in 99mTc-MIBI imaging were 80%, 95%, 88% in DeltaUR, and 74%, 74%, 74% in DeltaPI, respectively. The area under the receiver operator characteristic curve (A(z)) of the 99mTc-MIBI-DeltaUR (0.923) was significantly higher than that of DeltaPI (0.809, p = 0.025) but only marginally higher than that of the 201Tl-DeltaUR (0.865, p = 0.079). A(z) in 201Tl (0.865) was not significantly different from that of DeltaPI (0.809, p = 0.35). 99mTc-MIBI imaging performed in the middle of chemotherapy well predicts the final tumor response to chemotherapy in patients with malignant bone and soft tissue tumors.

Assessment of the Intestinal Permeability following Postoperative Chemotherapy for Human Malignant Disease

Purpose: Administration of anticancer drugs may damage gastrointestinal epithelium, thereby increasing the permeability of the gastrointestinal mucosa. We estimated the usefulness of oral lactulose and mannitol (L/M) test for assessment the extent of mucosal damage following postoperative chemotherapy for human malignant disease. Methods: The permeability index (PI): the urinary recovery ratio of excreted L to M was measured before and after chemotherapy in 31 patients with gastrointestinal cancers who underwent surgical resection. These findings were compared with data on 12 patients with breast cancer. The effect of chemotherapy was evaluated by the ratio of increase in PI, which was designed as post-chemotherapy value on day 7 divided by pre-chemotherapy value. Results: The mean PIs before chemotherapy in patients who underwent gastrectomy or colectomy were significantly higher than the value in those treated with mastectomy (p < 0.05). In the gastrointestinal cancer patients, the mean PIs significantly increased after chemotherapy compared with the pre-chemotherapeutic value (p < 0.01), however no significant difference was seen in breast cancer patients. When the ratios of increase in PI were calculated among gastric cancer patients, the total gastrectomy group showed a significantly higher increase in PI compared with the partial gastrectomy group (p < 0.05). Conclusions: Since the oral L/M absorption test is useful for assessing the degree of mucosal damage and measurement of intestinal permeability, this analysis should be recommended to determine the optimum timing and the adequate dosage of the anticancer drug administration.

Effect on natural killer and antibody-dependent cellular cytotoxicity of adjuvant cytotoxic chemotherapy including melphalan in breast cancer.

Natural killer (NK) cell activity and antibody-dependent (K) cell activity were studied sequentially in 30 patients with early node-positive breast cancer entered into an adjuvant chemotherapy trial. The drugs used were melphalan, and melphalan with methotrexate, given for 12 months. Estimations were made 3-monthly during chemotherapy, and then at 15 and 24 months to assess recovery. Mean values for NK-cell activity during chemotherapy were significantly lower than the mean pre-chemotherapy baseline value at all time-points from 3 to 15 months, but there was recovery by 24 months. Mean values for K-cell activity during chemotherapy did not appear to differ from the mean pre-chemotherapy value, but variability in individual values was high. Over a 4-year follow-up period, a comparison of 16 patients who did not develop recurrent breast cancer with 14 who did showed that NK-cell activity was significantly lower in the latter group 12 months after the start of chemotherapy.