Intensive Preoperative Chemotherapy Research Articles

Efficacy of thoracotomy and thoracoscopic-assisted esophageal surgery in conversion and salvage surgeries: a retrospective study

BackgroundThe esophagus has no serosa; therefore, esophageal cancer may quickly invade its adjacent organs. In recent years, reports of conversion surgery (CS) and salvage surgery (SS) have described resection of esophageal cancer previously considered unresectable, with the addition of intensive preoperative chemotherapy or chemoradiotherapy. Currently, there is no established method for determining whether tumor excision is possible. Additionally, differences in surgical approaches between facilities may influence outcome after resection. However, the option for resection is considered a significant factor in determining a patient’s prognosis.MethodsPatients who were diagnosed with advanced-stage (T3 or higher) squamous cell carcinoma of the esophagus and subsequently underwent resection with CS or SS were included in the study. Resection was performed through a small thoracotomy using a thoracoscope. Clinicopathologic factors, such as complete resection rate (R0) and prognosis, were investigated.ResultsA total of 49 surgeries were conducted: 39 CS and 10 SS cases. The male-to-female ratio was 37:12. R0:R1:R2 equals 42:3:4, and the R0 resection rate was 85.7%. The 5-year survival rates for CS and SS cases were 69.2% and 32.1%, respectively. The 5-year survival rates for R0, R1, and R2 resections were 63.4%, 0.0%, and 25.0%, and those for R0 and R1 + 2 resections were 63.4% and 14.3%, respectively, indicating that the prognosis for R0 resection cases was significantly better (P = 0.001 and P = 0.001, respectively). Regarding chemotherapy for CS, 29 patients received 5-FU and cisplatin therapy, whereas 10 patients received 5-FU, cisplatin, and docetaxel (DCF) therapy. After 2015, the ratio of DCF was significantly high, and the R0 resection rate was 100% in patients who received DCF therapy.ConclusionsIn this study, a satisfactory R0 rate was achieved using the magnifying effect of the thoracoscope while ensuring safety during thoracotomy.Trial registrationThis was a single-center cohort study wherein clinical data were retrospectively registered. This study was approved by the Chiba Cancer Center review board (H29-262). All procedures adhered to the ethical standards of the responsible committee on human experimentation and the Helsinki Declaration of 1964 and its later amendments.

Modern views on the problem of treatment of osteosarcoma of the extremities

According to the analysis results of the longterm treatment experience of more than 800 patients with osteosarcomas the authors began to perform the new record of the osteosarcoma treatment, the basic aims of which are the increase of the number of patients with promunced medicinal pathomorphism at the expence of more intensive preoperative chemotherapy. After chemotherapy intensification the incidence of side effects increases. The data on the osteosarcoma pathogenesis with the sexual steroid hormones are obtained. It is emphasized that the immediate and remote results of the extremity osteosarcoma treatment can be achieved only in the highly specialized centers provided with current diagnosis methods, treatment monitoring and supporting therapy measures.

Do arterial resections improve survival in pancreatic cancer?-a narrative review.

In this article, we outline the important features of pancreatic cancer surgery in cases with visceral artery encasement. Despite recent advances in diagnosis and treatment, pancreatic cancer continues to have a poor prognosis. Due to its limited response to chemotherapies, radiation, or targeted therapies, surgery (in combination with adjuvant chemotherapy) is the only potential way to treat pancreatic cancer in a curative manner. As only about 20% of the patients have surgically resectable disease at the time of diagnosis, the resection of encased visceral veins and arteries, along with neoadjuvant regimens, is one approach to treat otherwise palliative patients. Based on a selective literature review, we discuss the results of several studies and meta-analyses, comparing the mortality and morbidity, as well as long-term survival in patients undergoing arterial resection vs standard treatment. We conducted a selective literature review in PubMed without restrictions regarding time of publication or study design. Only articles in English language were selected. Several studies and meta-analyses comparing resection with and without arterial resection and reconstruction showed a significantly higher post-operative mortality and morbidity and shorter long-term survival in patients who required arterial resection. In patients with tumors initially considered irresectable, the approach of neoadjuvant chemotherapy followed by resection with arterial reconstruction showed a significantly increased survival compared to palliative chemotherapy alone with acceptable postoperative morbidity. Tumor resection with arterial reconstruction following intensive preoperative chemotherapy (plus radiochemotherapy in some cases) should be considered in selected patients, as it can prolong survival and potentially lead to sustained freedom from tumor recurrence.

Abstract PD7-01: Towards personalized medicine - patient-derived breast tumor grafts as predictors of relapse and response to therapy. Preliminary results

Abstract Background: Predicting the risk of relapse in patients with non-metastatic breast cancer is important for medical decisions and patient counseling. For patients who receive neoadjuvant chemotherapy, pathologic response and especially pathologic complete response (pCR) has been associated with risk of relapse; however this association is imperfect. Our prior work in patient-derived xenograft (PDX) models indicated that tumor engraftment in mice correlated with risk of recurrence. To understand further the prognostic utility of PDX, we designed a prospective clinical trial to determine the correlation between PDX generation with residual disease following neoadjuvant chemotherapy and relapse. Preliminary data are presented. Methods: Women with newly diagnosed non-metastatic hormone receptor low-positive (HR-low, ER and/or PR ≤ 10%) or negative breast cancer planned to receive systemic chemotherapy prior to definitive surgery were eligible. Tumor tissue at diagnosis was orthotopically implanted in NOD/SCID mice. The primary objective of the study is to correlate the ability of a tumor to engraft in mice with pathologic responses and clinical outcomes. Results: Between 12/2016 and 2/2020, 58 patients enrolled (triple negative breast cancer (TNBC), n=37; HR-low or negative/Her2+, n=11; or HR-low/Her2-, n=8; mixed, n=1). PDXs were successfully established from 16 patients. Patients uniformly received intensive preoperative chemotherapy per standard of care. Among the 12 patients whose tumors engrafted in mice (PDX(+)) and underwent surgery, the pCR rate was 41.7%. In the subgroup of patients with postoperative follow up >6 months (n=9), 3 patients had achieved a pCR, 1 of whom recurred; and 6 patients had residual disease, 3 of whom recurred (overall relapse rate 44.4%). All patients who relapsed (TNBC n=3; HR-low/Her2- n=1), experienced a very early relapse (<12 months) after their definitive surgery. Disease progressed to metastatic during preoperative chemotherapy in one patient and 2 patients with residual disease relapsed while on adjuvant capecitabine. One patient experienced an early relapse despite having achieved a pCR. Patients who relapsed, died of breast cancer ≤1 year after diagnosis; the only surviving patient has not reached this landmark yet. Among the 38 patients whose tumors did not engraft (PDX(-)) and underwent surgery, the overall pCR rate was 60.6%. In the subgroup of patients with postoperative follow up >6 months (n=30), 18 patients had achieved a pCR of whom none recurred, and 12 had residual disease of whom 1 patient (with TNBC) had locoregional recurrence 35.1 months after her definitive surgery (relapse rate 3.3%). She underwent repeat surgery followed by radiation therapy and 5.5 months after her recurrence, she remains disease-free. Achievement of pCR was not statistically different between the PDX(+) and PDX(-) group. In the entire cohort, the presence of residual disease was associated with high risk of relapse (22.2%) as compared to the achievement of pCR (4.8%, p = 0.16). However, successful tumor engraftment was associated not only with a higher risk of relapse (44.4% vs 3.3%, p = 0.0068, odds ratio 20.45), but also an early and exceptionally aggressive relapse. Conclusion. Our functional studies not only identify a patient population with a high risk of relapse with greater precision than the achievement of pCR, but also identify patients whose relapse has a particularly aggressive natural history. We established models that recapitulate this aggressive disease and in-depth genomic studies are underway. These studies will lead us to better patient stratification on the basis of risk of relapse and novel therapeutic strategies focused on patients with exceptionally aggressive breast cancers that our current diagnostic methods cannot identify. Citation Format: Christos Vaklavas, Zhengtao Chu, Rachel E Factor, Alana L Welm, Bryan E Welm, Cindy B Matsen. Towards personalized medicine - patient-derived breast tumor grafts as predictors of relapse and response to therapy. Preliminary results [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 PD7-01.

Significance of mesothelin expression in preoperative endoscopic biopsy specimens for colorectal cancer prognosis.

Mesothelin (MSLN) is a cell surface glycoprotein that is normally expressed in the mesothelial cells but highly expressed in several malignant tumors, where the high expression is generally associated with poor prognosis. In this work, 512 patients with stage III colorectal cancer (CRC) were examined to ascertain the prognostic value of MSLN expression in preoperative endoscopic biopsy specimens. MSLN expression was evaluated by immunohistochemical staining. The tumor cells were MSLN-positive in 61 of the 512 patients (11.9%). MSLN expression was associated with a shorter disease-specific survival (DSS) period (5-year DSS = 68.7%, P = 0.0008). Besides, by multivariate analysis, MSLN expression was identified to be a marker of poor prognosis by multivariate analysis (P = 0.0033, hazard ratio (HR) = 2.31) as well as macroscopic type (P = 0.047, HR = 1.82) among the factors that can be evaluated preoperatively. MSLN-positive patients had a significantly poorer prognosis regardless of adjuvant chemotherapy administration (P = 0.0081 and P = 0.0018 for surgery alone and chemotherapy, respectively). MSLN-positive patients in the adjuvant chemotherapy group exhibited a significantly lower risk of recurrence when compared with those in the surgery alone group (P = 0.0090). In conclusion, high MSLN expression observed in preoperative endoscopic biopsy specimens of stage III CRC was an independent poor prognostic factor. Preoperative evaluation of MSLN by immunohistochemical staining might be applied to select individuals for intensive preoperative chemotherapy among the stage III CRC patients.

Prognostic Value of Interval Between the Initiation of Neoadjuvant Treatment to Surgery for Patients With Locally Advanced Rectal Cancer Following Neoadjuvant Chemotherapy, Radiotherapy and Definitive Surgery.

Background: The addition of intensive preoperative chemotherapy and using of a longer waiting period between neoadjuvant radiotherapy and total mesorectal excision (TME) surgery lengthen the time interval from the initiation of neoadjuvant treatment to definitive surgery in patients with locally advanced rectal cancer (LARC). Here, we evaluated the prognostic value of different time intervals between the initiation of neoadjuvant treatment to TME surgery for LARC.Methods: A total of 2,267 patients with LARC, who received neoadjuvant radiochemotherapy and TME surgery, between January 2010 through December 2018 were recruited. The entire cohort was divided into 4 subgroups based on total-time-to surgery, defined as the time interval between initiation of neoadjuvant treatment and TME surgery (TTS): <13 weeks (TTS-1), 13 to <15 weeks (TTS-2), 15 to <17 weeks (TTS-3), ≥17 weeks (TTS-4). Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) rates in different TTS subgroup patients were compared, and hazard ratios (HR) for different demographic and clinicopathological variables, including TTS, were calculated to determine their prognostic significance.Results: The median follow-up time was 42.0 (range, 5–162) months. The 3-year OS, DFS, DMFS, and LRFS rates were 87.0, 79.4, 80.9, and 93.8%, respectively. The varied OS, DFS, and DFMS rates were detected among these different TTS subgroups (P = 0.010, P < 0.001, and P < 0.001, respectively). Particularly, the lower survival outcome was mainly observed at patients in the shortest TTS group (TTS-1). Cox regression analysis confirmed that the only significant positive independent prognostic factor for 3-year DFS was a longer TTS (TTS 2–4 vs. TTS-1; HR 0.884, 95% CI 0.778–0.921, P < 0.001), while the significant negative independent prognosticfactors were moderate to poor tumor differentiation (vs. well-differentiated; HR 1.191, 95% CI 1.004–1.414, P = 0.045) and clinical N1-2 stage (vs. N0 stage; HR 1.190, 95% CI 1.052–1.347, P = 0.006).Conclusion: For patients with LARC, an interval between the initiation of neoadjuvant treatment and TME surgery of longer than 13 weeks is associated with favorable disease-free survival.

Primary tumor location affects recurrence-free survival for patients with colorectal liver metastases after hepatectomy: a propensity score matching analysis

BackgroundWhether primary tumor location of colorectal cancer (CRC) affects survival of patients after resection of liver metastases remains controversial. This study was conducted to investigate the differences in clinicopathological characteristics and prognosis between right-sided CRC and left-sided CRC patients with liver metastases after hepatectomy.MethodsFrom 2002 to 2018, 611 patients with colorectal liver metastases (CRLM) who underwent hepatectomy at our center were reviewed. Primary tumors located from the cecum to transverse colon were defined as right-sided group (n = 141); tumors located from the splenic flexure to rectum were defined as left-sided group (n = 470). Patients were compared between two groups before and after a 1:1 propensity score matching (PSM) analysis.ResultsBefore PSM, median survival time and 5-year overall survival (OS) rate in right-sided group were 77 months and 56.3%, and those in left-sided group were 64 months and 51.1%, respectively. After PSM, median survival time and 5-year OS rate in right-sided group were 77 months and 55.9%, and those in left-sided group were 58.8 months and 47.3%, respectively. The OS rates did not differ between two groups before and after PSM (P = 0.575, P = 0.453). However, significant different recurrence-free survival (RFS) rate was found before and after PSM between right-sided and left-sided group (P = 0.028, P = 0.003).ConclusionsCompared to patients with left-sided primary tumors, patients with right-sided primary tumors had a worse RFS but similar OS. Careful preoperative evaluation, intensive preoperative chemotherapy, and frequent follow-up to detect early recurrence might be justified for CRLM patients with right-sided primary tumors.

PS02.101: PREOPERATIVE TREATMENT BASED ON THE DCF CHEMOTHERAPY AND SUPPORTIVE THERAPY FOR ESOPHAGEAL CANCER

Abstract Background The neoadjuvant chemotherapy using CDDP and 5-FU(CF) is the standard treatment for advanced esophageal cancer, defined as clinical stage II/III in Japan. However, more powerful chemotherapy has been required for the treatment of cases of cStageIII cases. In 2011, the combination treatment of CF and Docetaxel (DCF) was introduced for the treatment of those cases in our institute. DCF therapy increased chemotherapy remarkable cases. But, adverse events occur at high rates, including high myelosuppression. Therefore, it is necessary to ensure support by early intervention of supportive therapy so as not to exacerbate adverse events. We report about treatment outcome in preoperative DCF therapy cases. Methods We treated 128 esophageal cancer patients who underwent surgery following preoperative DCF therapy between 2011 and July 2017, and preoperative DCF was administered to 128 patients 2 course completely. The neoadjuvant chemotherapy regimen using DCF is Docetaxel:70mg/m2 (day1) + CDDP:70mg/m2 (day1) + 5-FU:700mg/m2 (day1–5). Results In the preoperative DCF group, overall response rate (over PR) was 51.5%. There were 37 cases in 128 cases of pathological tissue effect judgment for Grade 2 and 3. 14 cases of them (14cases/37cases:37.8%) had lymph node metastasis. Therefore it is necessary to control lymph node metastasis by surgery even in a remarkable group. Almost all patients experienced grade 4 adverse events, particularly neutropenia is a high frequency. From the start of chemotherapy, pretreatment of intraoral infection lesion and prevention and treatment of oral mucositis are performed. Considering the degree of myelosuppression during initial chemotherapy, in the second course, we actively administer G-CSF preparation. Conclusion A good prognosis can be expected if preoperative DCF therapy is effective. It is necessary to perform intensive and safe preoperative chemotherapy with appropriate supportive therapy intervention. Disclosure All authors have declared no conflicts of interest.

A case of successful preoperative chemotherapy with cisplatin and irinotecan followed by curative-intent surgery for locally advanced thymic carcinoma

The optimal chemotherapy for thymic carcinoma has yet to be determined based on clinical evidence because of the rarity of this pathological entity. We report the case of a patient with locally advanced thymic carcinoma in whom radical excision was achieved with intensive preoperative chemotherapy followed by curative-intent surgery. A 59-year-old woman was diagnosed with Masaoka-Koga stage III thymic cancer showing squamous cell carcinoma histology. Invasion to the ascending aorta and left brachiocephalic vein was suspected from imaging, so preoperative chemotherapy with three cycles of cisplatin and irinotecan was administered. Partial response to chemotherapy was achieved and the residual tumor was completely resected with subsequent surgery. Histopathological examination of the resected specimen demonstrated stage II thymic carcinoma. The patient has shown no evidence of recurrence or surgical complications as of 46months after completing preoperative chemotherapy.

What Is a Safe Future Liver Remnant Size in Patients Undergoing Major Hepatectomy for Colorectal Liver Metastases and Treated by Intensive Preoperative Chemotherapy?

A multidisciplinary approach involving preoperative chemotherapy has become common practice in patients with colorectal liver metastases (CLM). The definition of a safe future liver remnant (FLR) volume based on preoperative clinical data in these patients is lacking. Our aim was to identify predictors of postoperative morbidities in patients undergoing major hepatectomy after intensive preoperative chemotherapy for CLM. Between January 2000 and August 2010, a total of 101 consecutive patients with CLM underwent major hepatectomy after preoperative chemotherapy (≥6 cycles of oxaliplatin or irinotecan regimen with or without targeted therapies). The FLR ratio was calculated by two formulas: actual FLR (aFLR) ratio, and standardized FLR (sFLR) ratio. Predictors of postoperative overall morbidity, sepsis, and liver failure were identified by univariate and multivariate analyses. Fifty-eight patients (57.4%) had 95 postoperative complications. Sepsis and postoperative liver failure occurred in 23 (22.8%) and 16 patients (15.8%), respectively. On univariate analysis, small aFLR ratio was significantly associated with all complications, and sFLR ratio was associated with sepsis and liver failure. In receiver-operating characteristic analysis, the cutoff of aFLR ratio in predicting overall morbidity, sepsis, and liver failure was 44.8, 43.1, and 37.7%, respectively, and that of sFLR ratio in predicting sepsis and liver failure was 43.6 and 48.5%, respectively. On multivariate analysis, these aFLR and sFLR ratio cutoffs were independent predictors of all complications and of sepsis and liver failure, respectively. This study provides a cutoff FLR ratio for safe postoperative outcome after major hepatectomy in CLM patients receiving six or more cycles of preoperative chemotherapy.

European Organization for Research and Treatment of Cancer – Breast Cancer Group (EORTC BCG)

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by European Organization for Research and Treatment of Cancer – Breast Cancer Group (EORTC BCG). Clinical trials include: Postoperative adjuvant chemotherapy followed by adjuvant tamoxifen versus nil for node-negative and node-positive patients with operable breast cancer. EORTC Study No. 10901Randomized phase III study comparing short, intensive preoperative combination chemotherapy with similar therapy given postoperatively. EORTC Trial No. 10902Phase III randomized trial investigating the role of internal mammary and medial supraclavicular (IM-MS) lymph node chain irradiation in stage I–III breast cancer (joint study of the EORTC Radiotherapy Cooperative Group and the EORTC Breast Cancer Cooperative Group). EORTC Study No. 10925/22922A survey of the Breast International Group (BIG) to assess the attitude of patients aged &lt;35 years, with early breast cancer, toward the risk of loss of fertility related to adjuvant therapies. BIG 3-98/EORTC 10002LAMANOMA: Conservative local treatment versus mastectomy after induction chemotherapy in locally advanced breast cancer: a randomized phase III study. BIG 2-00/EORTC Study No. 10974/22002p53 study: First prospective intergroup translational research trial assessing the potential predictive value of p53 using a functional assay in yeast in patients with locally advanced/inflammatory or large operable breast cancer, prospectively randomized to a taxane versus non-taxane regimen. BIG 1-00/EORTC 10994After mapping of the axilla: radiotherapy or surgery AMAROS. EORTC 10981/22023A randomized phase II–III trial evaluating the efficacy of capecitabine and vinorelbine in anthracycline and taxane pretreated metastatic breast cancer. EORTC 10001/160010Phase I study of lonafarnib (SCH 66336) in combination with Herceptin plus paclitaxel in HER-2 neu overexpressing breast cancer. EORTC 10051/16023MINDACT trial: A prospective, randomized study comparing the Amsterdam 70-gene expression signature (Mammaprint) with common clinical pathological criteria in selecting patients for adjuvant chemotherapy in node-negative breast cancer. BIG 3-04/EORTC 10041

Midterm results with hepatectomy after preoperative chemotherapy in hepatoblastoma

We evaluated the results of surgical treatment for hepatoblastoma in infants and children after intensive preoperative chemotherapy, with special reference to histology and extent of liver involvement. The clinical features of 10 children with hepatoblastoma were reviewed regarding response to neoadjuvant chemotherapy, histological subtypes, extent of hepatectomy, operative complications, and prognosis. Response to chemotherapy was measured by volumetric assessment of tumour size by computed tomography scan. Cisplatin and Adriamycin (PLADO regime) up to three cycles markedly reduced the tumour volume on computed tomography (mean regression rate 65.9%); alpha-foetoprotein (AFP) levels also decreased from an initial mean of 16,116.4 ng/ml to 2,050.9 ng/ml. Five patients underwent right hepatectomy, two had right trisegmentectomy, two had left hepatectomy, and one had left trisegmentectomy. Histopathology of resected specimens revealed foetal histology in four patients, poorly differentiated (anaplastic) subtype in three, and mixed histology with mesenchymal components and osteoid formation in three. There was 100% resectability including six unresectable tumours (prechemotherapy). Moreover, hepatic resection tended to be less invasive in patients whose tumours had been much reduced after preoperative chemotherapy. Preoperative administration of cisplatin and Adriamycin reduces the tumour size significantly so that a safe radical hepatectomy can be performed. It also allows early administration of postoperative chemotherapy. Although overall good results were obtained with the current protocol, we also document our experience of unfavourable outcomes in patients with bilobar tumours (despite trisegmentectomy), patients with tumours showing poor response to neoadjuvant chemotherapy, and patients with anaplastic histology. Overall, at a 60-month follow-up we report an 80% survival rate by a combined approach.

Favorable outcome of Ewing sarcoma family tumors to multiagent intensive preoperative chemotherapy: A single institution experience

Aim of our study was to evaluate the efficacy of multiagent intensive preoperative chemotherapy in patients with Ewing sarcoma family tumors (ESFT), in order to succeed a better percentage of necrosis before surgical resection. Eighteen patients with ESFT were treated with the same multiagent intensive preoperative protocol. 5/18 patients had bone Ewings sarcoma (EWS) and 13/18 had peripheral primitive neuroectodermal tumor (PNET). None had metastases at diagnosis. Chemotherapy consisted of 5 or 6 cycles with vincristine, cisplatin, cyclophosphamide, and Adriamycin, followed by 12 cycles of vincristine, cyclophosphamide, and actinomycin-D. Five patients with EWS underwent total resection after 5-6 cycles of preoperative chemotherapy and prosthetic replacement was performed in two of them. In 3/13 patients with PNET the tumor was resected at diagnosis and in 1/13 after 5 cycles of chemotherapy, while 9/13 patients received chemotherapy only and/or radiotherapy. In patients with EWS, the histologic specimens of the resected tumors showed that tissue necrosis was 100% in four patients and 95% in one patient. The good histologic response reflects the effectiveness of this regimen in all ESFT. No patient had topical recurrence or developed metastatic disease during follow-up period (2-13 years, mean time 7.4 years). All patients had the scheduled cycles without delays or dose reductions. There were no major side effects of chemotherapy. The intensive chemotherapy schedule, comprising of 5-6 cycles preoperatively, seems to maximize the percentage of tumor necrosis, thus improving outcome. Our study implies that this combined therapy may improve the prognosis of ESFT.

Proliferation markers predictive of the pathological response and disease outcome of patients with breast carcinomas treated by anthracycline-based preoperative chemotherapy

The cell proliferation rate has been correlated to the response of breast carcinomas to preoperative chemotherapy (CT) and to disease outcome. However, this parameter is not yet used to select which tumours should be treated with preoperative CT. Furthermore, there is no consensus in the method used to evaluate cell proliferation. In poor prognosis breast carcinomas (PPBCs) treated by intensive preoperative CT, we compared the predictive value of S phase fraction (SPF), mitotic index (MI) and Ki67. We also evaluated the prognostic significance of the variation of the MI after CT. A series of 55 T2-T4N0N1M0 breast carcinomas were treated with 4 cycles of cyclophosphamide, 5-fluorouracil (5-FU) and doxorubicin. SPF was determined by flow cytometry on pre-therapeutic needle aspiration products. MI and Ki67 were evaluated on pre-therapeutic biopsy samples and on the tumours after CT. Fifteen patients (27%) had a pathological complete response (pCR), whereas 40 (73%) had residual disease. All three proliferative markers were found to have predictive value, but this value was higher for MI than for SPF ( P=0.04) and Ki67 ( P=0.03): the rate of pCR was 50% in cases with MI>17/3.3 mm 2, but was only 7% in cases with MI under this threshold ( P=0.0003). A significant decrease of MI (mean 10.97) was observed after CT ( P=0.001). Furthermore, we observed that even for patients with residual tumour, the variation of MI after CT was a prognostic parameter and overall survival. The sequential analysis of MI in breast cancers treated by preoperative CT thus provides a surrogate for predicting long-term outcome.

Long-term local intensive preoperative chemotherapy and joint-preserving conservative surgery for osteosarcoma around the knee.

This study evaluated conservative joint-sparing surgery for patients with osteosarcoma around the knee. Of 23 patients with stage IIB osteosarcoma around the knee, 5 were treated with long-term (30-56 weeks) local intensive preoperative chemotherapy consisting of high-dose methotrexate, intra-arterial and intravenous cisplatinum, doxorubicin, and hyperthermic isolated regional perfusion. More conservative resection, sparing the knee joint, was performed with smaller sufficient surgical margin in these 5 patients, preserving good limb function. Excellent local effects were achieved in the resected specimens. These results suggest long-term local intensive preoperative chemotherapy, including intra-arterial cisplatin and hyperthermic isolated regional perfusion, help control local tumor and allow for more conservative surgery.

Outcome of radiation-related osteosarcoma after treatment of childhood and adolescent cancer: a study of 23 cases.

We analyzed the clinical features and outcome of patients with radiation-associated osteosarcoma treated during the era of contemporary chemotherapy. The characteristics and outcome of 23 patients (17 males and six females) treated during childhood or adolescence for a solid tumor who later developed osteosarcomas within the radiation field between 1981 and 1996 were reviewed. The median dose of radiation delivered to the first cancer was 47 Gy. Nineteen patients also received chemotherapy. The median time between radiotherapy and the diagnosis of secondary osteosarcoma was 8 years. Histologic slide review showed conventional central osteosarcoma with various differentiation patterns in 21 cases, together with one case of high-grade surface osteosarcoma and one of periosteal osteosarcoma. The sites of involvement were the craniofacial bones in six cases, the first cervical vertebra in one, the girdle bones in seven, and the extremities of long bones in nine. Three patients had metastatic disease at the diagnosis of osteosarcoma. Palliative therapy was administered to seven patients. The aim of treatment was curative for 16 patients, two of whom underwent amputation without further therapy. Intensive chemotherapy regimens were administered to 14 patients before and/or after surgery. Fifteen patients achieved complete surgical remission. Twelve patients were alive and disease-free at a median follow-up duration of 7.5 years. Overall and event-free survivals at 8 years were 50% and 41%, respectively. Patients with radiation-related osteosarcoma and resectable lesions can be cured with surgery and intensive preoperative and postoperative chemotherapy.

Pulmonary metastases of stage IIB extremity osteosarcoma and subsequent pulmonary metastases.

This study investigated prognostic factors in nonmetastatic high-grade extremity osteosarcoma and the prognosis following resection of subsequent pulmonary metastases, with emphasis on the effect of chemotherapy-induced tumor necrosis. We reviewed 111 consecutive patients with high-grade nonmetastatic extremity osteosarcoma treated with preoperative chemotherapy and surgical resection, with additional review of 36 patients who had subsequent pulmonary metastases resected. The overall 5-year survival rate was 53%. In resected primary tumors, tumor-free resection margin (P < .001) and increasing chemotherapy-induced tumor necrosis (> 90% threshold, P < .003) correlated with increased metastasis-free survival. Relative risk factors for metastases were as follows: tumor-containing resection margin (most likely to metastasize); poor response to preoperative chemotherapy and/or lack of postoperative chemotherapy (next worse prognosis); and excellent response to preoperative chemotherapy (> or = 90% necrosis) combined with postoperative chemotherapy (best prognosis). The 5-year survival rate following pulmonary metastasis resection was 23%, whereas a 0% 4-year survival rate followed development of bony metastases (P < .001). The extent of tumor necrosis in resected pulmonary metastases did not affect prognosis. Survival was best in patients with three or fewer pulmonary nodules (P < .048), four or fewer recurrent pulmonary nodules (P < .047), unilateral pulmonary metastases (P < .037), or longer intervals between primary tumor resection and metastases (P < .082). Intensive preoperative and postoperative chemotherapy combined with complete resection of both primary and metastatic pulmonary osteosarcomas is justified, with a goal of 100% tumor necrosis and excision. Although current treatment regimens allow effective salvage therapy for a few patients with pulmonary metastases, more effective systemic treatment is needed.

Treatment Recommendations for Osteosarcoma and Adult Soft Tissue Sarcomas

During the past 20 years, dramatic improvements have been obtained in the treatment of localised osteosarcoma of the extremities, both in the rates of disease-free survival and in quality of life. Twenty years ago 80 to 90% of the patients died, in spite of mutilating surgery, but now about 75% survive and avoid the necessity of amputation. This is due to the introduction of very effective combined treatments, mostly also using preoperative chemotherapy. One of the major issues is that of intensive preoperative chemotherapy, which improves both limb salvage and survival. A multidisciplinary approach is necessary to obtain good results. When the role of adjuvant or neoadjuvant chemotherapy is not accurately defined for soft tissue sarcomas, particular emphasis is given to the staging of the diseases and to the important role of local treatment in the survival of these patients. A combination of radiation therapy and surgery is strongly recommended.

Intensive preoperative chemotherapy with colony-stimulating factor for resectable adenocarcinoma of the esophagus or gastroesophageal junction.

The curative resection rate in patients with potentially resectable carcinoma of the esophagus is approximately 55% and their median survival time is 11 months. Preoperative chemotherapy with high doses of chemotherapeutic agents was used to evaluate clinical and pathologic responses, curative resection rate, toxicity, and survival. Colony-stimulating factor (CSF) was added to reduce the severity of myelosuppression. Twenty-six consecutive assessable patients with potentially resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative courses of intensive chemotherapy (etoposide, doxorubicin, and cisplatin [EAP]) with granulocyte-macrophage CSF (GM-CSF). Additional three conventional-dose postoperative chemotherapy courses without GM-CSF were given to patients who responded to preoperative chemotherapy. A median of three courses (range, one to six), were administered. Of 27 patients, 26 were assessable for response to preoperative EAP; 13 (50%) achieved a major response. Among 23 patients who underwent surgery, 15 (65%) had a curative resection (58% of 26 assessable patients); none of the patients had a pathologic complete response, but two patients had only microscopic carcinoma in the resected specimen. Six patients had carcinoma present at the resection margins and received postoperative radiotherapy. Two patients were found to have liver metastases at exploration. At a median follow-up of 22 months, the median survival of 26 patients was 12.5 months (range, 2 to 32 +). Fourteen patients died of their carcinoma; two patients died of treatment-related causes; one died of an unrelated CNS arterial malformation; and the causes of death in two patients remain unknown. Seven patients are alive with no evidence of relapse. Major toxicities of this regimen included severe myelosuppression, nausea and vomiting, infections, and severe constitutional symptoms related to GM-CSF. However, subcutaneous injection of GM-CSF was well tolerated. High-dose EAP is active against locoregional adenocarcinoma of the esophagus and gastroesophageal junction but can be associated with significant toxicity. Although this strategy remains attractive and needs to be developed further, less toxic and more effective regimens need to be identified.

Mastectomy Following Preoperative Chemotherapy Strict Operative Criteria Control Operative Morbidity

The surgical morbidity associated with aggressive preoperative chemotherapy in 106 patients with advanced primary breast cancer who had chemotherapy followed by mastectomy was examined. These patients were compared with a group of 91 consecutive patients who had mastectomy without preoperative chemotherapy. Strict operative criteria were used to determine the timing of mastectomy following chemotherapy. Wound infection rates were no different in the preoperative chemotherapy group compared to the mastectomy-alone groups (7% versus 4%; p = 0.62). The incidence of wound necrosis was similar (11% versus 6%; p = 0.29). Seroma formation was decreased significantly in the preoperative chemotherapy group compared to the mastectomy-alone group (15% versus 28%; p = 0.04). Intensive preoperative chemotherapy did not delay the reinstitution of postoperative treatment (30% versus 20%; p = 0.27). However, when delay in instituting postoperative chemotherapy was more than 30 days, there was a significant decrease in overall survival rate (p = 0.04). This study provides evidence that intensive preoperative chemotherapy and mastectomy can be performed without increased morbidity. Furthermore it is important to institute systemic chemotherapy within 30 days of mastectomy to achieve maximum survival.