Weeks Of Preoperative Chemotherapy Research Articles

Outcomes of Wilms tumor treatment in western Kenya.

Wilms tumor (WT) is a curable type of cancer with 5-year survival rates of over 90% in high-income countries, whereas this is less than 50% in low- and middle-income countries. We assessed treatment outcomes of children with WT treated at a large Kenyan teaching and referral hospital. We conducted a retrospective record review of children diagnosed with WT between 2013 and 2016. Treatment protocol consisted of 6weeks of preoperative chemotherapy and surgery, and 4-18weeks of postoperative chemotherapy depending on disease stage. Probability of event-free survival (pEFS) and overall survival (pOS) was assessed using Kaplan-Meier method with Cox regression analysis. Competing events were analyzed with cumulative incidences and Fine-Gray regression analysis. Of the 92 diagnosed patients, 69% presented with high-stage disease. Two-year observed EFS and OS were, respectively, 43.5% and 67%. Twenty-seven percent of children died, 19% abandoned treatment, and 11% suffered from progressive or relapsed disease. Patients who were diagnosed in 2015-2016 compared to 2013-2014 showed higher pEFS. They less often had progressive or relapsed disease (p=.015) and borderline significant less often abandonment of treatment (p=.09). Twenty-nine children received radiotherapy, and 2-year pEFS in this group was 86%. Outcome of children with WT improved over the years despite advanced stage at presentation. Survival probabilities of patients receiving comprehensive therapy including radiation are approaching those of patients in high-income countries. Additional improvement could be achieved by ensuring that patients receive all required treatment and working on earlier diagnosis strategies.

Outcome of Stage IV Completely Necrotic Wilms Tumour and Local Stage III Treated According to the SIOP 2001 Protocol.

Simple SummaryAround 15–20% of all Wilms tumour (WT) patients present with metastatic disease. Approximately 10% of these patients achieve complete necrosis after preoperative chemotherapy, which is associated with a favourable prognosis. The aim of this observational study is to describe the outcome of metastatic patients with completely necrotic (low-risk histology), local stage III WT treated according to the SIOP 2001 protocol, whether or not postoperative radiotherapy was applied.Objective: Wilms tumour (WT) patients with a localised completely necrotic nephroblastoma after preoperative chemotherapy are a favourable outcome group. Since the introduction of the SIOP 2001 protocol, the SIOP– Renal Tumour Study Group (SIOP–RTSG) has omitted radiotherapy for such patients with low-risk, local stage III in an attempt to reduce treatment burden. However, for metastatic patients with local stage III, completely necrotic WT, the recommendations led to ambiguous use. The purpose of this descriptive study is to demonstrate the outcomes of patients with metastatic, completely necrotic and local stage III WT in relation to the application of radiotherapy or not. Methods and materials: all metastatic patients with local stage III, completely necrotic WT after 6 weeks of preoperative chemotherapy who were registered in the SIOP 2001 study were included in this analysis. The pattern of recurrence according to the usage of radiation treatment and 5 year event-free survival (EFS) and overall survival (OS) was analysed. Results: seven hundred and three metastatic WT patients were registered in the SIOP 2001 database. Of them, 47 patients had a completely necrotic, local stage III WT: 45 lung metastases (11 combined localisations), 1 liver/peritoneal, and 1 tumour thrombus in the renal vein and the inferior vena cava with bilateral pulmonary arterial embolism. Abdominal radiotherapy was administered in 29 patients (62%; 29 flank/abdominal irradiation and 9 combined with lung irradiation). Eighteen patients did not receive radiotherapy. Median follow-up was 6.6 years (range 1–151 months). Two of the 47 patients (4%) developed disease recurrence in the lung (one combined with abdominal relapse) and eventually died of the disease. Both patients had received abdominal radiotherapy, one of them combined with lung irradiation. Five-year EFS and OS were 95% and 95%, respectively. Conclusions: the outcome of patients with stage IV, local stage III, completely necrotic Wilms tumours is excellent. Our results suggest that abdominal irradiation in this patient category may not be of added value in first-line treatment, consistent with the current recommendation in the SIOP–RTSG 2016 UMBRELLA protocol.

The Effect of Time-to-Surgery on Outcome in Patients with Neurological Deficits Caused by Spinal Tuberculosis.

To compare and analyze the influence of the duration of neurological symptoms and degree of neurological deficits on the postoperative neurological recovery of patients with neurological deficits caused by spinal tuberculosis (TB). We retrospectively reviewed the data of 47 adult patients with neurological deficits caused by spinal TB. They were divided into three and four groups according to the duration of neurological symptoms and degree of neurological deficits, respectively. Differences in the mean rank within groups were statistically evaluated, and logistic regression of the two factors was performed to evaluate how these factors influence the recovery of neurological function. Non-parametric tests indicated a significant difference among improvement grades in the three groups based on the duration of neurological symptoms (p < 0.05). No significant difference was found among improvement grades of the patients preoperatively in the four groups based on the grade of neurological deficits (p > 0.05). Logistic regression showed that the preoperative grade of neurological deficits significantly influenced the improvement grade of neurological deficits (p < 0.05), but the correlation was not close (R2=0.28). The duration of neurological symptoms, but not the grade of neurological involvement, is correlated with postoperative neurological recovery of patients with neurological deficits caused by spinal TB. However, reducing preoperative chemotherapy does not significantly yield improved outcomes; therefore, undergoing four weeks of preoperative chemotherapy is acceptable.

A splenic volume increase due to preoperative chemotherapy may impair the long-term outcome after hepatectomy in patients with initially non-optimally resectable colorectal cancer liver metastases.

In patients with colorectal cancer liver metastases (CRCLM), chemotherapy-associated hepatotoxicity (CAH) has been shown to be associated with splenomegaly. The aim of the present study was to investigate whether a higher splenic volume increase (SVI) after preoperative chemotherapy was associated with a worse long-term outcome after hepatectomy in patients with CRCLM. Between 2007 and 2012, there were 36 patients who received preoperative chemotherapy based on a diagnosis of initially non-optimally resectable synchronous CRCLM. The splenic volume was measured by CT-volumetry before preoperative chemotherapy and 12 weeks after the start of the chemotherapy. Long-term outcome was analyzed in these patients. The overall survival was significantly shorter in the SVI ≥30% group than in the SVI <30% group (3-year survival = 52% vs. 28%, p <0.05). The disease-free survival was also significantly shorter in the SVI ≥30% group than in the SVI <30% group (Median = 11 vs. 6 months, p <0.05). The survival after recurrence was significantly shorter in the SVI ≥30% group than in the SVI <30% group (Median = 12.0 vs. 18 months, p<0.05). In patients with non-optimally resectable CRCLM, the SVI during the first 12 weeks of preoperative chemotherapy may be a significant predictor of the long-term survival after hepatectomy.

Ki-67 Index Guided Selection of Preoperative Chemotherapy for HER2-positive Breast Cancer: A Randomized Phase II Trial

Changes in Ki-67 may be a useful predictor of efficacy for preoperative therapy in breast cancer. This randomized Phase II trial will compare standard preoperative chemotherapy comprising paclitaxel and trastuzumab with Ki-67 index guided preoperative chemotherapy in patients with human epidermal growth factor receptor 2-positive operable breast cancer. In the Ki-67 index guided therapy, paclitaxel and trastuzumab were administered initially and the Ki-67 index is evaluated from biopsied specimens after 2 weeks of preoperative chemotherapy. The subsequent chemotherapy regimen is modified according to changes in the Ki-67 index from the start of therapy. If the Ki-67 index is reduced as expected, paclitaxel and trastuzumab are continued. If the Ki-67 index is not reduced as expected, the chemotherapy regimen is changed to epirubicin, cyclophosphamide and trastuzumab. The primary endpoint is the rate of pathological complete response. The secondary endpoints are the objective response rate, disease-free survival and overall survival. Two hundred patients were planned to be accrued.

Preoperative Chemotherapy With Doxorubicin in Wilms Tumor

Vincristine and actinomycin-D have long been used as the preoperative chemotherapy before nephrectomy in patients with Wilms tumor (WT). Actinomycin-D is not readily found in Turkey, and delay in treatment, occurring basically from commercial and marketing problems, prompted us to administer alternatives such as doxorubicin, another antitumor antibiotic available in Turkey, to our newly diagnosed patients with WT. Between November 2009 and January 2011, 12 consecutive patients with WT were included in the study. Preoperative chemotherapy consisted of vincristine (1.4 mg/m, days 1, 8, 15, and 22) and doxorubicin (20 mg/m, 1 to 3 d). All renal tumors showed shrinkage drastically after 4 weeks of preoperative chemotherapy. Surgery of all the patients was uneventful and without any complications. At the end of the median follow-up time of 8 months (range, 6 to 17 mo), all patients are in remission without a sign of the disease. Preoperative chemotherapy consisting of vincristine and doxorubicin seems to be successful as a preoperative treatment in achieving shrinkage and reducing the risk of surgical complications. On the basis of the promising results in our study, it is worth administering a similar regimen with further follow-up in larger populations.

Veno‐occlusive disease as a complication of preoperative chemotherapy for Wilms tumor: A clinico‐pathological analysis

Vincristine (VCR) and actinomycin D (ACD) form the backbone of chemotherapeutic regimens of Wilms tumor treatment. Veno-occlusive disease (VOD) is a potentially life-threatening complication of ACD. To investigate the incidence of VOD after preoperative chemotherapy and assess the effect of dose and frequency of administrating ACD on the occurrence of VOD. A single-center retrospective study of patients where liver biopsies were performed after 4 or 8 weeks of preoperative chemotherapy. Patients had localized or metastatic Wilms tumor and were treated according to SIOP 9, 93-1, or 2001 protocol. A correlation was analyzed between histologically confirmed VOD, laboratory parameters, and mode and frequency of ACD administration. Long-term hepatic toxicity was assessed 5 years after the end of therapy. Ninety-one patients were included in this analysis. Forty-one patients (45.1%) had histological evidence of VOD. The incidence of histologically proven VOD was significantly correlated with single administration of 45 microg/kg ACD (SIOP 2001 protocol) as compared to repeated dosing of l5 microg/kg (P = 0.003). Fifty-two percent of all patients had mild-to-severe abnormal liver enzymes 5 years after accomplishing therapy. Despite short-course preoperative chemotherapy regimen, patients are at risk of developing histological VOD. This risk is higher when ACD is administered in a 1-day 45 microg/kg regimen as compared to 3 days l5 microg/kg.

Acute malnutrition is common in Malawian patients with a Wilms tumour: A role for peanut butter

Children with cancer in resource limited countries are often malnourished at diagnosis. Acute malnutrition is associated with more infectious complications and an increased risk of morbidity and mortality in major surgery. All new patients with the clinical diagnosis of a Wilms tumour admitted in the Queen Elizabeth Central Hospital, Blantyre, Malawi from January 2007 until June 2008 were included. We documented anthropometric parameters, tumour size and serum levels of micronutrients at diagnosis. Corrected weight (body weight - tumour weight) was repeated after 4 weeks of preoperative chemotherapy. During therapy oral feeds were encouraged and a locally made ready to use therapeutic peanut butter-based food (chiponde) supplied. A high rate of acute malnutrition was found in patients with Wilms tumour at diagnosis (45-55%), much higher than in community controls (11%). Patients (40%) and community controls (37%) had a similar, high rate of stunting (low height for age), a sign of chronic malnutrition. Tumour size at diagnosis and the degree of acute malnutrition at diagnosis was correlated; patients with a larger tumour had more severe acute malnutrition (r = -0.88, P < 0.01). With a supply of chiponde, 7 of 18 patients had a >5% increase in corrected weight during preoperative chemotherapy. Patients with a more positive nutritional course had a better tumour response to chemotherapy (r = 0.52, P < 0.05). Surprisingly, few micronutrient deficiencies were found, except for low serum levels of vitamin A (44% of patients). Acute malnutrition, superimposed on chronic malnutrition, is common in patients with Wilms tumour in Malawi. Earlier presentation needs to be encouraged. Chiponde, a peanut butter based ready-to-use-therapeutic-food, is an attractive means of nutritional support which needs further study.

Therapy for Osteosarcoma

Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. Current optimal treatment for osteosarcoma consists of multi-agent chemotherapy and aggressive surgical resection of all sites of disease involvement. The current national and international cooperative trial for patients with newly diagnosed osteosarcoma builds upon the backbone of cisplatin, doxorubicin, and methotrexate. This protocol is designed to clarify whether (i) the addition of ifosfamide and etoposide to postoperative chemotherapy with cisplatin, doxorubicin, and methotrexate improves the event-free survival and overall survival for patients with resectable osteosarcoma and a poor histologic response to 10 weeks of preoperative chemotherapy; and (ii) the addition of pegylated interferon-alpha-2b as maintenance therapy after postoperative chemotherapy with cisplatin, doxorubicin, and methotrexate improves the event-free survival and overall survival for patients with resectable osteosarcoma and a good histologic response to 10 weeks of preoperative chemotherapy. However, the optimal treatment strategy (or strategies) for patients with relapsed or metastatic disease has yet to be defined. This remains one of the persistent challenges in the treatment of osteosarcoma. Recent therapeutic advances have focused on circumventing chemotherapy resistance mechanisms, incorporation of non-classical agents into upfront therapy, targeting of the tumor micro-environment, and investigating the role of novel delivery mechanisms. In patients with localized disease the 5-year survival rate is at least 70%; patients with metastatic or recurrent disease have <20% chance of long-term survival despite aggressive therapies. These figures have changed little in the past 2 decades. This review focuses on the current therapy for osteosarcoma, and highlights emerging strategies that will hopefully change the outlook for patients with this disease.

Immediate nephrectomy versus preoperative chemotherapy in the management of non-metastatic Wilms’ tumour: Results of a randomised trial (UKW3) by the UK Children’s Cancer Study Group

Purpose: To determine if patients receiving preoperative chemotherapy with vincristine and actinomycin D for non-metastatic Wilms’ tumour have a more advantageous stage distribution and so need less treatment compared to patients who have immediate nephrectomy, without adversely affecting outcome. Methods: Between 1991 and 2001, a total of 205 patients with newly diagnosed non-metastatic renal tumours, of which 186 had Wilms’ histologies, were randomly assigned either to immediate surgery or to 6 weeks preoperative chemotherapy and then delayed surgery. Both groups of children received postoperative chemotherapy according to tumour stage and histology determined at the time of nephrectomy. Results: There was a significant improvement in the stage distribution for patients with Wilms’ histologies receiving delayed surgery compared to those having immediate nephrectomy (stage I: 65.2% versus 54.3%; stage II: 23.9% versus 14.9%; stage III: 9.8% versus 29.8%, χ 2 test for trend = 7.02, p = 0.008). This improvement resulted in 20% fewer children receiving radiotherapy or doxorubicin yet event-free and overall survivals at 5 years of 79.6% and 89.0%, respectively, were similar in the two groups. Conclusion: Six weeks of preoperative chemotherapy with vincristine and actinomycin D results in a significant shift towards a more advantageous stage distribution and hence reduction in therapy, while maintaining excellent event free and overall survival in children with non-metastatic Wilms’ tumour. Around 20% of survivors were therefore spared the late-effects of doxorubicin or radiotherapy. Our results suggest that all children with non-metastatic Wilms’ tumour should receive chemotherapy prior to tumour resection.

Commentary on Wilms' tumour

WILMSI TUMOUR is one of the success stories of modern oncology, as clearly discussed in Dr Green’s Update in this issue of the European Journal of Cancer (pages 409-4 18). However, these achievements in the treatment of Wilms’ tumour should not detract from the sometimes very malignant course of the disease. As such, it is still very important that prognostic factors of the disease are better defined. Adaptation of treatment according to these factors will contribute to improved survival rates for the high risk patients, and a better quality of life from less therapy for those with intermediate and low risk disease. Early detection could also improve the outcome of children with Wilms’ tumour. Since Wilms’ tumour is associated with some well known congenital syndromes, screening for Wilms’ tumour has been considered in these high-risk children [I]. Thus far, there is no real evidence to support screening in this population, but since the screening method is easy to apply and tolerable for the patients, it could be recommended that high-risk children are followed up to their seventh or eighth year by sonography, initially every 34 months, extending this to every 6 months later on. In some of these children, early detection may make partial nephrectomy possible. Dr Green’s Update succinctly describes current methods of pretherapy staging of patients with Wilms’ tumour, particularly in the U.S.A. In Continental Europe, staging procedures are somewhat different, with clinical staging carried out at diagnosis, followed by 4 weeks of pre-operative chemotherapy. Surgical and pathological stages are determined after the neo-adjuvant chemotherapy. Another major difference is the fact that contrast enhanced computed tomography (CT) of the abdomen is not part of the routine clinical examination in SIOP protocols. The very low number of incorrect diagnoses reported in recent SIOP studies (1.5%), as well as some other points raised in the Update, justifies this policy. Furthermore, in a climate where cost-effectiveness has to be considered, CT-scanning is an expensive procedure, which may limit its use in some institutions. Because it is important that protocols for Wilms’ tumour from large study groups should be applicable in centres all

Effects of preoperative chemotherapy on gastric adenocarcinomas. A morphologic study of 25 cases.

Surgical neoadjuvant therapy for gastric adenocarcinoma affords the opportunity to evaluate critically the histologic effects of preoperative chemotherapy. Morphologic alterations in gastric adenocarcinomas were examined in the surgical-resection specimens from 25 patients after 6 weeks of preoperative chemotherapy. The group included 1 patient with a complete response; 4, with subtotal responses; 4, with partial responses; and 16, with no response to preoperative chemotherapy. Histologic manifestations of preoperative chemotherapy included mucosal edema, aggregates of histiocytes in the submucosa and muscularis externa, and stromal fibrosis of the submucosa and muscularis externa. Cytologic manifestations were uncommon and included a single case of signet ring cell carcinoma with diminution of the cytoplasmic vacuoles after preoperative chemotherapy. Clinical follow-up was limited, but 3 of the 25 patients died within 5-8 months after the diagnosis of gastric adenocarcinoma. The gastric-resection specimens from these three patients did not show any histologic manifestations of preoperative chemotherapy. As in tumors at other sites, the efficacy of surgical neoadjuvant therapy for gastric adenocarcinoma can be assessed, based on the histologic response of the resected tumor to preoperative chemotherapy.

Neoadjuvante Chemotherapie des Osteosarkoms

The neoadjuvant study COSS-86 was undertaken aiming at (1) improving the cure rate in osteosarcoma by early intensification of chemotherapy in high risk patients and (2) investigating the effect of intraarterial (i.a.) versus intravenous (i.v.) administration of cisplatinum. (1) Ifosfamide was added to the well proven drugs in osteosarcoma such as doxorubicin, high-dose methotrexate and cisplatinum in patients with large tumor size or/and high portion of chondroid groundsubstance or/and scintigraphic nonresponse after 4 weeks of preoperative chemotherapy. It was given in combination with cisplatinum. (2) The same patients were allocated to either the intraarterial study arm or the intravenous control arm of the study. The response rate (greater than 90% tumor necrosis) of all patients was 75% (88/118). No advantage in response rate was achieved by i.a. infusion of cis-platinum within this highly efficient 4-drug regimen (i.a. 75% (33/44) vs. i.v. 74% (35/47)). The significantly improved response rate in this study results in a better metastasis free survival (MFS) of 77% (+/- 4) at 4 years.

The impact of delayed surgery on radiotherapy dose and local control of rhabdomyosarcoma.

To determine if delayed surgery permits the modification of radiotherapy dose while maintaining local control in children with localized, unresectable rhabdomyosarcoma, a prospective study was launched in 1981 to test this objective. Treatment consisted of 16 weeks of preoperative chemotherapy, with or without delayed surgery, and radiotherapy using 35 to 40 Gy (3500 to 4000 rad) for microscopic and 50 to 55 Gy (5000 to 5500 rad) for gross residual tumor, plus 14 months of chemotherapy. Among 22 patients treated, surgery was feasible in 11 of 14 patients with residual tumor after chemotherapy and was performed in eight (avoiding radical surgery in three), leaving microscopic (seven patients) or gross residual (one patient) tumor. Progressive disease or amputation precluded radiotherapy in two patients. After radiotherapy local control was sustained in 12 of 14 patients with microscopic lesions vs none of six patients with gross tumor. Delayed surgery may permit the use of lower-dose radiotherapy and should be considered in the treatment plan for this subset of patients.