Neoadjuvant Chemotherapy

Classification of breast cancer into molecular subtypes maybe important for the proper selection of therapy, as tumors with seemingly similar histopathological features can have strikingly different clinical outcomes. Herein, we report the development of a molecular subtyping profile (BluePrint), that enables rationalization in patient selection for either chemotherapy or endocrine therapy prescription. An 80-Gene Molecular Subtyping Profile (BluePrint) was developed using 200 breast cancer patient specimens and confirmed on four independent validation cohorts (n = 784). Additionally, the profile was tested as a predictor of chemotherapy response in 133 breast cancer patients, treated with T/FAC neoadjuvant chemotherapy. BluePrint classification of a patient cohort that was treated with neoadjuvant chemotherapy (n = 133) shows improved distribution of pathological Complete Response (pCR), among molecular subgroups compared with local pathology: 56% of the patients had a pCR in the Basal-type subgroup, 3% in the MammaPrint Low-risk, Luminal-type subgroup, 11% in the MammaPrint Highrisk, Luminal-type subgroup, and 50% in the HER2-type subgroup. The group of genes identifying Luminal-type breast cancer is highly enriched for genes having an Estrogen Receptor binding site proximal to the promoterregion, suggesting that these genes are direct targets of the Estrogen Receptor. Implementation of this profile may improve the clinical management of breast cancer patients, by enabling the selection of patients who are most likely to benefit from either chemotherapy or from endocrine therapy.

570 patients with osteosarcoma of the extremities were treated with ®ve dierent protocols of neoadjuvant chemotherapy at Rizzoli Institute between 1983 and 1995. Surgery consisted of limb salvage in 83% rotation plasty in 5% and amputation in 12%. The 5-year event-free survival (EFS) was 60% which varied according to the protocol followed, ranging from 47.6% to 66.4%. 234 patients relapsed. The pattern of relapse was analysed. The mean relapse time was 23.8 months (range: 2±96). The ®rst site of systemic relapse was the lung in 88% (32% of these had less than three pulmonary metastases and 68% three or more), bone in 9%, lung and bone in 2% and other sites in 3%. The relapse time and the number of pulmonary metastases were strictly correlated with the ecacy of the protocol of chemotherapy used. Patients treated with the three protocols that gave a 5-year EFS of more than 60% relapsed later and had fewer pulmonary lesions than patients treated with the two protocols that gave a 5-year EFS of 47.6% and 52.5%. The rate of local recurrence was relatively low (6%). This was not correlated with the protocol or the type of surgery used: limb salvage (6.4%), rotation plasty or amputation (4.1%). However, the rate of local recurrence was very high (21.9%) in the few patients (7%) that had less than wide surgical margins. We conclude that for patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy: (a) the pattern of systemic relapse changes according to the ecacy of the protocol of chemotherapy used. This should be always considered when evaluating the preliminary results of new studies as well as in de®ning the time of follow-up; (b) limb salvage procedures are safe and do not jeopardise the outcome of the patient, provided that wide surgical margins are achieved.

The choice of palliative treatment and the prognostic factors in unresectable head and neck cancer cases continue to be controversial. In the present study we compared the survival rates of untreated stage IV head and neck cancer patients with cases managed prospectively at A.C. Camargo Hospital for Cancer with neoadjuvant chemotherapy, concomitant chemotherapy or radiotherapy alone. Previous results had shown that while the type of treatment did not influence survival rates (P = 0.706), tumor response to treatment (whether complete, partial or none) significantly influenced survival (P = 0.00002). In the present study we compared the survival rates in the groups with untreated patients (who remained untreated until death) with the same demographic and clinical characteristics of patients receiving treatment. We found that there was a significant difference between the survival rates of the untreated group and those of the treated groups that was independent of the type of treatment performed (P < 0.00001) or the tumor response to treatment (P < 0.0001).

Neoadjuvant chemotherapy has shown some success in the treatment of gastric carcinoma, but objective parameters for measuring its effects are lacking. The authors performed the current study to determine which histomorphologic features are correlated with patient prognosis after chemotherapy.

of FNA used in these cases helped to establish the diagnosis of IBC in 4 women presenting with a diffusely enlarged and tender breast, resulting in the timely initiation of appropriate management. The technique needs to be assessed in a larger cohort of women with diffusely enlarged breast to evaluate its diagnostic utility.

Wilms tumor is the most common renal malignancy in children. In the 1930s, overall survival for children with Wilms tumor was approximately 30%. Use of multidisciplinary therapy, guided by results from multiinstitutional, randomized trials, has substantially improved overall survival to about 90%. Management of Wilms tumor differs substantially between Europe and the US. In Europe, the International Society of Pediatric Oncology protocols call for management of patients with presumptive Wilms tumor with neoadjuvant chemotherapy followed by nephrectomy and further chemotherapy. In the US, protocols developed by the National Wilms Tumor Study Group advise primary nephrectomy followed by a chemotherapy regimen tailored to the pathologic tumor stage. Despite these disparate strategies, overall survival is similar in patients managed according to European and US protocols. Patients with Wilms tumor now have excellent survival. Therefore, current goals aim to reduce the morbidity associated with therapy. Important complications of treatment for Wilms tumor include cardiomyopathy, renal failure, and increased risk of a secondary malignancy. Currently, the role of laparoscopic surgery in management of Wilms tumor remains extremely limited.

Metformin may reduce the incidence of breast cancer and enhance response to neoadjuvant chemotherapy in diabetic women. This trial examined the effects of metformin on Ki67 and gene expression in primary breast cancer. Non-diabetic women with operable invasive breast cancer received pre-operative metformin. A pilot cohort of 8 patients had core biopsy of the cancer at presentation, a week later (without treatment; internal control), then following metformin 500mg o.d. for one week increased to 1g b.d. for a further week continued to surgery. A further 47 patients had core biopsy at diagnosis, were randomized to metformin (the same dose regimen) or no drug, and 2 weeks later had core biopsy at surgery. Ki67 immunohistochemistry, transcriptome analysis on formalin fixed paraffin embedded cores and serum insulin determination were performed blinded to treatment. 7 patients (7/32, 21.9%) receiving metformin withdrew due to gastrointestinal upset. The mean percentage of cells staining for Ki67 fell significantly following metformin treatment in both the pilot cohort (p=0.041, paired t-test) and in the metformin arm (p=0.027, Wilcoxon rank test) but was unchanged in the internal control or metformin control arms. Messenger RNA expression was significantly down-regulated by metformin for PDE3B (phosphodiesterase 3B, cGMP-inhibited; a critical regulator of cAMP levels which affect activation of AMP-activated protein kinase, AMPK), confirmed by immunohistochemistry, SSR3, TP53 and CCDC14. By Ingenuity Pathway Analysis, the Tumour Necrosis Factor Receptor 1 (TNFR1) signaling pathway was most affected by metformin: TGFB, MEKK were up-regulated and cdc42 down-regulated; mTOR and AMPK pathways were also affected. Gene Set Analysis additionally revealed that p53, BRCA1 and cell cycle pathways also had reduced expressed following metformin. Mean serum insulin remained stable in patients receiving metformin but rose in control patients. This trial presents biomarker evidence for anti-proliferative effects of metformin in women with breast cancer and provides support for therapeutic trials of metformin.

Primary systemic therapy (PST) or neoadjuvant therapy is used in nonmetastatic breast cancer to treat systemic disease earlier, decrease tumor bulk ideally to a complete pathological response (pCR), and reduce the extent of surgery. The multitude of clinical trials using PST in breast cancer patients has not proven the fundamental hypotheses of improved overall survival and disease-free survival that drove the investigation of PST. The other potential advantages of PST, which include increasing the rate of breast-conserving surgery and predicting outcome to a particular chemotherapy regimen, are also not conclusively established. We examined the published literature on PST for breast cancer and predominantly focused our review on data from large, randomized clinical trials comparing primary systemic chemotherapy with adjuvant chemotherapy, different primary systemic chemotherapy regimens, primary systemic chemotherapy with hormonal therapy, and different preoperative hormonal therapies. Although the optimal neoadjuvant chemotherapy regimen has not been established, a combination of four cycles of an anthracycline followed by four cycles of a taxane appears to produce the highest pCR rate (22%-31%). In patients with HER-2-positive breast cancer, concurrent use of neoadjuvant trastuzumab with an anthracycline-taxane combination has produced provocative results that require further confirmatory studies. Preoperative hormonal therapy is associated with low pCR rates and should be reserved for patients who are poor candidates for systemic chemotherapy. The optimal management of patients with residual disease after the administration of maximum neoadjuvant therapy remains to be defined. The surgical approach, including the role of sentinel node biopsy and delivery of radiation therapy after PST in breast cancer patients, is evolving. Ongoing clinical trials will help identify the subset of patients who would most benefit from the use of PST, establish the most effective PST regimen, and determine the optimal multidisciplinary approach in the management of breast cancer. The Oncologist 2006;11:574-589

Reçu le 19 novembre 2002 ; reçu en forme révisée le 17 mars 2003 ; accepté le 19 mars 2003 Résumé Objectifs. -Le cancer du sein survenant chez la femme très jeune est rare et son diagnostic et sa prise en charge sont parfois difficiles. L'objectif de l'étude était d'en analyser les caractéristiques épidémiologiques et clinicopathologiques et surtout d'évaluer les résultats des thérapeutiques instaurées. Patientes et méthodes. -Les dossiers de trente patientes âgées de 30 ans ou moins, chez qui un diagnostic de cancer invasif du sein a été porté entre 1986 et 2001, ont fait l'objet d'une étude rétrospective dans le service de radiothérapie du centre Alexis-Vautrin. Résultats. -Six patientes (20 %) avaient un antécédent familial de cancer mammaire. Dans 90 % des cas, le signe révélateur était un nodule cliniquement palpable, de taille moyenne de 3,5 cm. Il s'agissait de 11 cancers de stade I, 11 de stade II, de 6 de stade III et de deux de stade IV. Cinq cancers ont été découverts au décours d'une grossesse (taille clinique moyenne = 5,8 cm). Une chimiothérapie néoadjuvante a été prescrite chez 11 patientes. Vingt trois fois sur 28 (82 %), le sein a pu être conservé. Il s'agissait d'un carcinome canalaire infiltrant de grade III dans 13/27 cas et une fois sur deux, il s'accompagnait d'une atteinte ganglionnaire axillaire. Les récepteurs oestrogéniques étaient absents dans 11/26 cas. Après un suivi post-thérapeutique médian de 5 ans, on a constaté six récidives locales (20 %), quatre cancers du sein controlatéral et trois cancers secondaires. Dix patientes (38 %) sont décédées dans un tableau d'évolution métastatique ultérieure. Le taux de survie globale à 5 ans était de 78 %. Conclusion. -Ces résultats rejoignent les données de la littérature qui soulignent le pronostic défavorable du cancer du sein chez les femmes très jeune et incitent à adapter en fonction de l'ensemble des facteurs pronostiques les indications des thérapeutiques locales et des traitements adjuvants systémiques et hormonaux. © 2003 Éditions scientifiques et médicales Elsevier SAS. Tous droits réservés.

La incidencia de las metástasis cerebrales en el cáncer de ovario es baja. Presentamos el caso de una paciente de 48 años con carcinoma serosopapilar de ovario bilateral. Se decide quimioterapia neoadyuvante, cirugía citorreductora de rescate y radioterapia pelviana, por ser subóptima la cirugía. A los 9 años presenta una recidiva pleural que se resuelve con 6 ciclos de carbotaxol. A los 11 años presenta una metástasis cerebral de 8 cm, que se extirpa, y se administra tratamiento complementario con radioterapia holocraneal y boost sobre el lecho quirúrgico. Actualmente, la paciente está asintomática y sin secuelas. En pacientes con metástasis cerebral única, la cirugía, seguida de radioterapia y quimioterapia sistémica, ofrece los mejores resultados.

Locally advanced breast cancer is a clinical quandary for which there is no standard treatment regimen. Often, preoperative chemotherapy regimens are chosen from proven regimens recommended for the adjuvant setting, as accepted by national panels. There are several accepted characteristics of breast tumors that may predict greater response to neoadjuvant chemotherapy, including phenotype, nuclear grade, and proliferation index. The following cases illustrate two clinical situations in which the neoadjuvant chemotherapy given yielded partial to near complete responses, yet left questions for the clinician regarding the optimum approach to best reduce the risk of recurrence.

Purpose. To prospectively compare the ability of clinical examination, mammography, vascularity-sensitive ultrasound, and magnetic resonance imaging (MRI) to determine pathologic complete response (CR) in breast cancer patients undergoing neoadjuvant chemotherapy.

Neoadjuvant systemic therapy (NST) has become part of the standard treatment of patients with locally advanced breast cancer. Patients who achieve a pathologically complete response (pCR) after NST have improved outcomes compared with patients with residual disease at the primary tumor site or the lymph nodes. Achieving a pCR after NST correlates with improved disease-free and overall survival; therefore the amount of residual disease is a prognostic predictor, and it is an area of ongoing research. In this article, we review the literature on NST to highlight the importance of pCR as a prognostic indicator. We also review the defi nition of pCR and describe the association between different patient and tumor characteristics, including the breast cancer subtype classifi cation, and its response to chemotherapy. We expand on the clinical impact of residual disease and comment on the importance of quantifying it and the current treatment recommendations for patients with residual disease after NST.

La incidencia de masas anexiales en la gestación es de 1 por 1.000 embarazos; de ellos, el 3% son malignos. La mayoría de estas masas son asintomáticas y el diagnóstico se realiza frecuentemente mediante un hallazgo casual en la ecografía obstétrica; lo más común es que sea en el segundo trimestre. El manejo de los tumores ováricos depende de su naturaleza y clínica. En los casos en que se sospeche malignidad es necesaria una cirugía de estadificación e incluso asociar quimioterapia. En estos casos, debe intentarse conservar la fertilidad. Presentamos 2 casos de teratomas inmaduros de ovario en gestantes.

The role of neoadjuvant chemotherapy in locally advanced breast cancer is firmly established. There is now also an emerging role for neoadjuvant systemic therapy in the treatment of operable breast cancer. There is good evidence that the chances of breast conserving surgery can be increased with this approach and results of randomised studies indicate that survival is at least as good with neoadjuvant as with adjuvant chemotherapy. Similar clinical data are emerging with neoadjuvant endocrine therapy. For the future, there are important potential advantages in having an in vivo measure of chemosensitivity rather than blindly treating micrometastatic disease in the adjuvant setting.

75 patients with locally advanced cervical carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stages IB-111) received three courses of neoadjuvant chemotherapy (NAC), including cisplatin, bleomycin, and methotrexate (PBM). Fifteen percent of patients achieved a complete response (CR) and 68% a partial response (PR). Pretreatment characteristics were analyzed for response to NAC. Significantly lower response rates were found in patients with tumor size more than 5 cm in diameter and bilateral parametrial involvement to the pelvic side wall. None of the biological parameters studied was related to chemoresponsiveness. Patients achieving CR or PR had a significantly improved %year survival rate compared with those who did not respond. After NAC, radical surgery was possible in all responding patients. The median number of lymph nodes removed was 60. A lower than expected incidence of lymph node metastases was detected. None of the clinical and pathologic features considered was significantly correlated with the lymph node status. Twelve of the 62 operated patients had disease recurrence. Pathologic parametrial involvement and cervical infiltration equal to or deeper than 5 mm were found to be significant prognostic factors for recurrence. A 3-year, disease-free survival of 89%, 7370, and 43% for Stage IB-IIA, IIB, and 111, respectively, was found. Among the operated patients these rates increased to 100%,8l%, and 66% for Stage IB-IIA, IIB, and 111, respectively. A prospective randomized trial comparing NAC and surgery with radiotherapy alone is in progress. Cancer 67:372-379,1991. N THE LAST FEW YEARS, neoadjuvant chemotherapy I has been applied as a new therapeutic approach of locally advanced cervical cancer because of the disappointing results with conventional treatment^.'-^ In fact the recent advances in radiotherapy techniques and surgery,

Background There is scarce data on the outcome of young patients aged 35 years and younger, who have been treated with neoadjuvant chemotherapy. The aim of this study is to evaluate the impact of body mass index (BMI) and various prognostic factors on pathologic response and survival in young patients with localized breast cancer. Patients and methods This is a retrospective evaluation on the outcome of 110 patients who were younger than 35 years at diagnosis and treated with neoadjuvant chemotherapy (CT). Patients were grouped in quartiles of BMI calculated prior to initiation of chemotherapy. Logistic regression analysis was performed to investigate the associations between prognostic variables including BMI and treatment outcome. The impact of prognostic factors on survival was analyzed by Kaplan-Maier and Cox regression tests. Results Body mass index was not correlated with pathologic complete response (pCR) (n = 13, 11.7%) or survival. Cox regression analysis revealed nodal pCR following neoadjuvant chemotherapy (HR 2.45, P = 0.048) and stage at diagnosis (HR1.99, P = 0.027) as signiWcant independent prognostic factors for DFS, while recurrence was independently associated with shorter OS (HR 169, P = 0.029).

Neoadjuvant chemotherapy (NAC) for breast cancer is evolving and subsequent adjuvant systemic treatment is mainly based on the presence of the Estrogen (ER) receptor, Progesterone (PR) receptor and Human Epidermal growth factor Receptor 2 (HER2) status on the core needle biopsy prior to treatment. It is not well known whether these biomarkers change after NAC, requiring a change in further adjuvant systemic treatment. A review of the literature (PubMed search) revealed 32 relevant studies that investigated the concordance of the hormone receptors (ER and/or PR) and HER2 after NAC with or without trastuzumab. Discordance of the hormone receptor status was reported in four out of eight studies in 8-33% of the patients. About half of the studies that tested the ER and PR receptor status separately reported discordances of 2.5-17% and 5.9-51.7% respectively. Studies that concluded that ER and/or PR receptor remained stable after NAC were performed with evidently lower number of patients compared to studies that reported a change. Good concordance of the HER2 amplification tested with FISH was reported, although the HER2 expression measured with immunohistochemistry was more discordant. A switch to a negative HER2 receptor in up to 43% of the patients was reported when NAC was combined with trastuzumab.

This study was designed to evaluate the benefits of neoadjuvant chemotherapy prior to chemoradiation and surgery in patients with locally advanced rectal cancer. Patients with previously untreated primary rectal cancer, reviewed in a multidisciplinary meeting and considered to have locally advanced disease on the basis of physical examination and imaging (MRI+CT n ¼ 30, CT alone n ¼ 6), were recruited. Patients received protracted venous infusion 5-FU (300 mg m À2 day À1 for 12 weeks) with mitomycin C (MMC) (7 mg m À2 i.v. bolus every 6 weeks). Starting on week 13, 5-FU was reduced to 200 mg m À2 day À1 and concomitant pelvic radiotherapy 45 Gy in 25 fractions was commenced followed by 5.4 -9 Gy boost to tumour bed. Surgery was planned 6 weeks after chemoradiation. Postoperatively, patients received 12 weeks of MMC and 5-FU at the same preoperative doses. Between January 99 and August 01, 36 eligible patients were recruited. Median age was 63 years (range ¼ 40 -85). Following neoadjuvant chemotherapy, radiological tumour response was 27.8% (one CR and nine PRs) and no patient had progressive disease. In addition, 65% of patients had a symptomatic response including improvement in diarrhoea/constipation (59%), reduced rectal bleeding (60%) and diminished pelvic pain/tenesmus (78%). Following chemoradiation, tumour regression occurred in 80.6% (six CRs and 23 PRs; 95% CI ¼ 64 -91.8%) and only one patient still had an inoperable tumour. R0 resection was achieved in 28 patients (82%). When compared with initial clinical staging, the pathological downstaging rate in T and/or N stage was 73.5% and pathological CR was found in one patient. Neoadjuvant systemic chemotherapy as a prelude to synchronous chemoradiation can be administered with negligible risk of disease progression and produces considerable symptomatic response with associated tumour regression.

Purpose The aim of this study was to describe magnetic resonance imaging (MRI) patterns in 21 patients with histologically proven invasive lobular cancer (ILC) of the breast. Materials and methods We retrospectively reviewed MR images of 21 out of 24 women with ILC of the breast. Three women were excluded from the study because they underwent neoadjuvant chemotherapy after MRI. Thirteen of the 24 women had positive clinical findings. All 24 patients underwent mammography, sonography and MRI. MRI was performed to evaluate disease extent and multifocality/multicentricity before modified radical mastectomy (n=5) or quadrantectomy (n=16). Two experienced radiologists reviewed the MRI scans and described the tumour patterns. Results We identified five morphological patterns of ILC: a solitary mass with irregular margins (n=8); a mass with smooth margins (n=5); multiple small enhancing foci with interconnecting enhancing strands (n=4); dominant lesion surrounded by small foci (n=3); one MR examination was negative. Conclusions Architectural and dynamic features are important in the interpretation of breast MRI findings. ILC may be detected on MRI as solitary or multiple lesions that correspond to tumour morphology on pathologic examination. False-negative MRI findings do occur in a small percentage of ILC. Obiettivo Descrivere le caratteristiche RM di 21 pazienti con carcinoma lobulare della mammella (ILC) istologicamente confermato. Materiali e metodi Sono state retrospettivamente valutate le immagini RM di 21 su 24 donne portatrici di ILC della mammella. Tre donne sono state escluse dallo studio, in quanto sottoposte a chemioterapia neo-adiuvante dopo l’indagine RM. Tredici donne su 24 presentavano una obiettività clinica. Tutte le 24 pazienti sono state sottoposte a mammografia, ecografia della mammella ed RM. RM è stata effettuata per valutare l’estensione locale di malattia e l’eventuale presenza di multifocalità o multicentricità, prima che le pazienti fossero sotttoposte a mastectomia radicale modificata (n=5) o quadrantectomia (n=16). Due radiologi esperti in diagnostica senologica hanno rivisto le immagini RM e descritto i patterns morfologici delle lesioni tumorali riscontrate. Risultati Sono stati riscontrati 5 patterns morfologici di ILC: una formazione espansiva singola a bordi irregolari (n=8); una formazione espansiva singola a bordi netti (n=5); piccoli foci multipli di impregnazione contrastografica interconnessi tra loro (n=4); una formazione espansiva principale circondata da piccoli foci satelliti (n=3); una indagine RM negativa. Conclusioni Le caratteristiche morfologiche e dinamiche sono importanti nell’interpretazione della RM mammaria. ILC può essere identificato dalla RM sulla base della presenza di lesioni solitarie o multiple, che corrispondono ai reperti anatomo-patologici. Indagini RM negative sono rare, ma possibili in una bassa percentuale di ILC.

Tratamento conservador dos carcinomas de mama localmente avançados T2 e T3, após quimioterapia neoadjuvante, com quadrantectomia e braquiterapia de alta taxa de dose como reforço de dose, teleterapia complementar e quimioterapia adjuvante Breast conserving treatment of locally advanced carcinoma T2 and T3 after neoadjuvant chemotherapy followed by quadrantectomy and high dose-rate brachytherapy, as a boost, complementary teletherapy and adjuvant chemotherapy Resumo Objetivo: avaliar o tratamento de carcinomas de mama T2 e T3(T>= 4 cm.), por quimioterapia neoadjuvante (Qt Neo), quadrantectomia e braquiterapia de alta taxa de dose (BAT) como reforço de dose (boost), radioterapia complementar e quimioterapia adjuvante, quanto às complicações do método, os resultados estéticos, o controle local, a sobrevida global (SG) e a sobrevida livre de doença (SLD). Pacientes e Métodos: Trata-se de estudo clínico prospectivo descritivo, que consistiu na avaliação de 26 pacientes com idade variando entre 30 e 70 anos, portadoras de carcinoma ductal infiltrante, nos estádios clínico (EC) IIB e IIIA, responsivas à Qt Neo. As complicações precoces e tardias da radioterapia foram avaliadas segundo critérios estabelecidos pelos grupos RTOG/EORTC (Radiotherapy and Oncology Group /European Organisation for Research and Treatment of Cancer). A avaliação estética foi feita por critérios estabelecidos pelo cirurgião plástico. O controle local foi avaliado por método clínico, mamografia e ultra-sonografia. A SG e a SLD foram analisadas segundo método de Kaplan-Meier. Todas as pacientes foram tratadas no Instituto do Câncer Dr. Arnaldo Vieira de Carvalho, no período de junho de 1995 a novembro de 2001, e avaliadas em março de 2002, com mediana de avaliação de 28,7 meses. Resultados: Complicações precoces da radioterapia foram observadas em oito pacientes (30,6%). Duas delas (7,6%) classificadas como G3 e G4 (RTOG/EORTC). Seis pacientes apresentaram complicações tardias e três (11,5%) foram classificadas como G3 e G4. Uma paciente (3,8%) apresentou recidiva local (RL) 64 meses após o tratamento. A avaliação estética foi considerada regular e boa em 16 (60,5%) de 24 pacientes analisadas. A SG e a SLD em 24, 36 e 60 meses foram 100%, 92,3% e 83,1% respectivamente. Conclusão: Os índices de complicações da radioterapia, tanto precoces quanto tardias, foram consideradas altas, quando comparados aos da literatura,mas os resultados estéticos foram considerados aceitáveis. A RL, a SG e a SLD são comparáveis a outras formas de tratamento. Palavras-chave: Neoplasias mamárias; Carcinoma; Tratamento conservador; Radioterapia; Braquiterapia. Artigo Original Tratamento conservador do câncer de mama localmente avançado Artigo submetido em 18/10/04; aceito para publicação em 20/03/05 Revista Brasileira de Cancerologia 2005; 51(2): 125-133 126 Revista Brasileira de Cancerologia 2005; 51(2): 125-133 Fristachi CE, et al

BACKGROUND.The objective of this study was to determine whether patients with breast cancer who received breast-conservation therapy after neoadjuvant chemotherapy had improved outcomes if radiopaque clips were placed to mark the primary tumor.The objective of this study was to determine whether patients with breast cancer who received breast-conservation therapy after neoadjuvant chemotherapy had improved outcomes if radiopaque clips were placed to mark the primary tumor.METHODS.The authors retrospectively reviewed the records of 410 patients with nonmetastatic breast cancer who received doxorubicin-based neoadjuvant chemotherapy and breast-conservation therapy from January 1990 to September 2005. Thirty-seven of those patients were omitted because of the inability to verify radiopaque clip placement in the primary tumor.The authors retrospectively reviewed the records of 410 patients with nonmetastatic breast cancer who received doxorubicin-based neoadjuvant chemotherapy and breast-conservation therapy from January 1990 to September 2005. Thirty-seven of those patients were omitted because of the inability to verify radiopaque clip placement in the primary tumor.RESULTS.Of the 373 patients who were analyzed, 145 patients had radiopaque clips placed to mark the primary tumor before or during neoadjuvant chemotherapy, and 228 patients did not. The distribution of clinical T classification, nuclear grade, estrogen receptor status, final margin status, and extent of residual primary disease was similar between the 2 groups. After a median follow-up of 49 months (range, 20-177 months), 21 patients developed a local recurrence in the treated breast. The 5-year rate of local control was 98.6% in patients who had radiopaque clips placed versus 91.7% in patients who did not have tumor marker clips placed (P = .02; log-rank test). On multivariate analysis, the omission of tumor bed clips was associated with a hazard ratio of 3.69 for increased local recurrence compared with patients who did have radiopaque clip placement (P = .083; 95% confidence interval, 0.84-16.16).Of the 373 patients who were analyzed, 145 patients had radiopaque clips placed to mark the primary tumor before or during neoadjuvant chemotherapy, and 228 patients did not. The distribution of clinical T classification, nuclear grade, estrogen receptor status, final margin status, and extent of residual primary disease was similar between the 2 groups. After a median follow-up of 49 months (range, 20-177 months), 21 patients developed a local recurrence in the treated breast. The 5-year rate of local control was 98.6% in patients who had radiopaque clips placed versus 91.7% in patients who did not have tumor marker clips placed (P = .02; log-rank test). On multivariate analysis, the omission of tumor bed clips was associated with a hazard ratio of 3.69 for increased local recurrence compared with patients who did have radiopaque clip placement (P = .083; 95% confidence interval, 0.84-16.16).CONCLUSIONS.The placement of radiopaque clips in patients who were receiving neoadjuvant chemotherapy and breast-conservation therapy was associated with better local control independent of stage and other clinicopathologic findings. The authors concluded that the placement of tumor-marker clips should be an integral part of the multidisciplinary approach in appropriate patients. Cancer 2007. © 2007 American Cancer Society.The placement of radiopaque clips in patients who were receiving neoadjuvant chemotherapy and breast-conservation therapy was associated with better local control independent of stage and other clinicopathologic findings. The authors concluded that the placement of tumor-marker clips should be an integral part of the multidisciplinary approach in appropriate patients. Cancer 2007. © 2007 American Cancer Society.

Background Recently, Architectural distortion (AD) has been detected via ultrasonography (US) even in the absence of a definitive mass; however, the clinical significance of this finding is yet unknown. The purpose of this study is to elucidate the causes of AD, as revealed by US. Methods Breast echo was undergone by 931 patients between January and December 2005. The study comprised 45 patients (4.8%) in the age range of 28-76 years (mean 49.8 years) whose images revealed AD despite the absence of mass formation. To investigate the causes of this AD, we retrospectively reviewed the medical records of these patients.

Aims and objectives: The aim of this paper was to study the impact of neoadjuvant chemoradiation on downstaging of locally advanced rectal carcinoma, sphincter saving procedures and toxicity profile of chemoradiation.
Method: 31 patients were studied who had locally advanced adenocarcinoma of rectum. They were treated preoperatively with 20 frations of 225 cGy (5 days/wk) radiation (total of 45Gy over 28 days). Chemotherapy consisted of 5-FU (500mg/m.sq) only for day 1, 2, & 3. After an interval of of 4-6 wks, all patients were submitted to surgery.The principles of TME was
Results: The median follow up in our study was 1year. At 1 year the overall survival in operated cases was 100% with no disease relapse. 67% of patients underwent low anterior resection,6.5% had proctosigmoidectomy with end colostomy,16.5% had a palliative surgical procedure, 6.5% became non compliant after neoadjuvant and 3.2% expired preoperatively during chemoradiation. At the time of surgery 82.6% of patients had pathological downstaging of tomour and 45.4% had lymphnode downstaging.Consequently 67.7% of patients underwent a sphincter preserving surgical procedure.
The incidence of complication was 29% with grade 2 mucositis and 9.7% with grade 1 mucositis. Myelosuppression was seen in non.
Conclusion: Significant downstaging of disease was seen with this regime of treatment and with improved subsequent sphincterv preserving procedures with acceptable toxicity profile.

Background: A wide variation in the accuracy of performance of sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy in breast cancer has been reported despite its increased use. This study aimed to be the first to evaluate the feasibility and accuracy of SLNB after neoadjuvant chemotherapy in Chinese patients with breast cancer. Methods: A review of prospectively collected data from breast cancer patients who had SLNB after prior neoadjuvant chemotherapy was performed. A combination of radiopharmaceutical 99mTc-albumin colloid (Pharmalucence, MA, USA) and Patent Blue V dye (Guerbet, France) was used to identify the SLN. SLNB was followed by standard axillary dissection in all patients. Results: A total of 365 patients received SLNB from May 1999 to April 2006. A total of 78 patients with neoadjuvant chemotherapy followed by SLNB were recruited. The SLN identification rate, false-negative rate and accuracy rate were 83.3, 10.3 and 73.1%, respectively. Analysis was stratified into clinical and pathological response group. Location of the tumour was also found to be an important factor in affecting the false-negative rate (P = 0.019). For upper, outer quadrant tumour, five (32.3%, out of 16) patients presented with false-negative. Patients with more sentinel lymph node harvest had higher accuracy. A total of 22 patients had three or more lymph nodes harvested, and the false-negative rate was 21.7% (5 out of 23 patients) (P = 0.00). Conclusions: The results of our study show that SLNB is feasible and applicable in Chinese patients with breast cancer with operable disease who have received neoadjuvant chemotherapy.

Approximately 70% of women with epithelial ovarian cancer (EOC) are diagnosed with advanced stage disease, which is associated with high morbidity and mortality. The standard approach to treating patients with advanced EOC remains primary debulking surgery (PDS) followed by chemotherapy. EOC is one of the most sensitive of all solid tumors to cytotoxic drugs, with over 80% of women showing a response to standard chemotherapy combined with taxane and platinum. Furthermore, residual disease is a major prognostic factor for survival. On the basis of the clinical features, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is considered to be an alternative treatment option to standard treatment in patients unable to undergo complete resection during PDS. Noninferiority of NACT-IDS to PDS has been demonstrated in some randomized controlled trials and meta-analyses. NACT would also lead to improved quality of life (QOL) of patients, however there are still problems to be solved in the treatment strategy. The uncertainty of perioperative visual assessment of tumor dissemination after NACT has been reported. In addition, several papers have shown the possibility that NACT induces platinum resistance. Furthermore, a notable risk associated with NACT is that patients with significant side effects and refractory disease will lose the opportunity for debulking surgery. Appropriate selection of the patient cohort for NACT is an important issue. Bevacizumab (Bev) is active in patients with advanced EOC. However, the use of Bev is not recommended in the neoadjuvant setting. Bev has a specific adverse event profile that needs to be considered, especially for surgical management, such as gastrointestinal perforation, hemorrhage, and thromboembolic events. NACT could be an alternative treatment option in patients with stage III or IV EOC. However, further studies are needed to clarify the precise role of NACT in the management of advanced EOC.

L'IRM est la technique la plus sensible pour la détection d'un cancer du sein. Chez des patientes avec un diagnostic de cancer, l'ajout de l'IRM n'est justifié qu'en cas de traitement conservateur envisagé et lorsque le cancer est occulte (ganglions axillaires métastatiques, maladie de Paget du mamelon), le cancer est non évaluable par l'imagerie standard, devant une suspicion d'atteinte pariétale, et en cas de traitement néoadjuvant. Dans les seins clairs, l'IRM n'est pas recommandée ; ses performances ne diffèrent pas significativement de celles de l'imagerie standard. En cas de seins denses, l'IRM est significativement plus sensible que la mammographie dans la détection d'une multifocalité et multicentricité avec une valeur prédictive positive des lésions additionnelles de l'ordre de 60 %. Ainsi, l'indication d'une mastectomie ne pourra être décidée sur les seules données de l'IRM (nécessité de pouvoir réaliser des repérages préopératoires ou des biopsies sous guidage IRM en cas de négativité de l'échographie ciblée). L'ajout de l'IRM doit s'adresser préférentiellement au groupe de patientes à haut risque de récidive locale, soit : un jeune âge (<40 ans), un contexte familial à haut risque, ou du fait d'un cancer invasif supérieur à 2 cm et de haut grade histopronostique. Réaliser des examens IRM dans cette population implique une équipe radiologique experte, des protocoles IRM optimaux, et une collaboration efficiente avec l'équipe thérapeutique multidisciplinaire. © 2007 Elsevier Masson SAS. Tous droits réservés.

To compare changes in the concentration of choline-containing compounds (tCho) and in tumor size at follow-up after neoadjuvant chemotherapy (NAC) between patients who achieved pathologic complete response (pCR) and those who did not (non-pCR).

Breast neoplasms Neoadjuvant therapy Lymphatic metastasis Lymph node excision Sentinel lymph node biopsy A B S T R A C T Aims: The purpose of this study is to analyse nodal staging and axillary response in breast cancer patients treated with neoadjuvant chemotherapy (NAC) to explore venues to safely spare patients axillary clearance whenever it could be avoided.

Background: Although surgical resection currently is the preferred treatment for fit patients with resectable esophageal cancers, it is associated with a relatively high risk of morbidity and significant perioperative mortality. Currently, a range of open surgical approaches are used. More recently, minimally invasive approaches have become feasible, with the potential to reduce perioperative morbidity. This study investigated the outcomes from one such approach. Methods: Outcome data were collected prospectively for 36 consecutive patients who underwent a minimally invasive esophagectomy for esophageal cancer. A threestage approach was used, with all the patients undergoing a thoracoscopic esophageal mobilization, combined with either open or hand-assisted laparoscopic abdominal gastric mobilization, and open cervical anastomosis. An open abdominal approach was used for 15 of the patients and a hand-assisted laparoscopic approach for 21. A total of 34 patients had invasive malignancy, whereas 2 had preinvasive disease. A group of 23 patients (68%) who had invasive malignancies also received neoadjuvant chemotherapy and radiotherapy. Results: The mean operating time ranged from 190 to 360 min (mean, 263 min). The median postoperative hospital stay was 16 days. In-hospital mortality was 5.5% (2/36), and perioperative morbidity was 41%. The perioperative outcomes for patients undergoing an open abdominal approach and those who had hand-assisted laparoscopic surgery were similar. For the patients who underwent a hand-assisted laparoscopic abdominal procedure, the total operating time was shorter (248 vs 281 min), and the blood loss was less (223 vs 440 ml). The median follow-up period was 30 months. The 4-year survival predicted by Kaplan-Meir for the 34 patients with invasive malignancy was 44%. Conclusion: The outcome for esophagectomy using thoracoscopic esophageal mobilization, with or without hand-assisted laparoscopic abdominal surgery, was comparable with data from conventional open surgical approaches. These approaches can be performed with an acceptable level of perioperative morbidity. Further application of these techniques, with close scrutiny of outcome data, is appropriate.

Primary malignant lymphoma of the cervix is a rare disease. Because the number of reports of this cancer is limited, there is no consensus on its management, prognosis or the efficacy of various treatments. Primary malignant lymphoma of the cervix stage Ib was diagnosed in a 25-year-old woman. The patient was treated with 6 courses of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone). Clinical and pathological responses were complete. This case supports current thinking in that, in selected young patients with primary malignant lymphoma of the cervix who desire to preserve fertility and ovarian functions, combination chemotherapy regimens such as CHOP are the treatment of choice.

months. Progression-free survival was significantly improved in patients achieving pCR (p = 0.001). Conclusions: pCR is associated with a better outcome regardless of clinical and pathological parameters in breast cancer patients who receive NAC. The probability of pCR was higher in ER-negative, LVI-negative tumors and in patients treated with sequential taxane-containing chemotherapy.

Diffuse WHO grade II (GIIG) may be unresectable when involving critical structures. To assess the feasibility and functional tolerance (cognition and quality of life) of an original therapeutic strategy combining neoadjuvant chemotherapy followed by surgical resection for initially inoperable GIIG. Ten patients underwent Temozolomide for unresectable GIIG, as initial treatment or at recurrence after previous partial resection, due to invasion of eloquent areas or bi-hemispheric diffusion preventing a total/subtotal removal. Functional outcome after both treatments was assessed, with evaluation of seven cognitive domains. Chemotherapy induced tumor shrinkage (median volume decrease 38.9%) in ipsilateral functional areas in six patients and in the contralateral hemisphere in four. Only four patients had a 1p19q codeletion. The tumor shrinkage made possible the resection (mean extent of resection 93.3%, 9 total or subtotal removals) of initially inoperable tumors. Postoperatively, three patients had no deficits, while verbal episodic memory and executive functions were slightly impaired in seven patients. However, global quality of life was roughly preserved on the EORTC QLQ C30 ? BN 20 (median score: 66.7%). Role functioning score was relatively reduced (median score: 66.7%) whereas KPS was preserved (median score: 90, range 80-100). Seven patients became seizure-free while three improved. This combined treatment is feasible, efficient (surgery made possible by neoadjuvant

Background  The lack of objective documentation of pre-neoadjuvant chemotherapy (NACT) margins after chemotherapy is a major constraint in performing safe breast-conserving surgery (BCS) in patients with locally advanced breast cancer (LABC). Using a novel method of marking pre-NACT tumor margins with indigenous silver wire markers, this prospective pilot study attempted to assess the feasibility of safe BCS in LABC patients by

Purpose: Treatment of extremity soft-tissue sarcomas yields excellent local control, but distant failure is common with large, high-grade tumors. A regimen of preoperative chemotherapy consisting of mesna, adriamycin, ifosfamide, and dacarbazine (MAID) interdigitated with radiotherapy followed by resection and postoperative chemotherapy with or without radiotherapy was designed to improve treatment outcome. We report the mature outcome data on 48 treated patients and compare them with the data of an historical matched control patient population. Methods and Materials: Adult patients with high-grade extremity soft-tissue sarcomas >8 cm were treated with three cycles of preoperative chemotherapy combined with 44 Gy of radiotherapy followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy was delivered postoperatively. Results: All 48 patients (M0) received the MAID protocol treatment, and their outcome was superior to that of the historical control patients. The 5-year actuarial local control, freedom from distant metastasis, disease-free survival, and overall survival rate was 92% and 86% (p ‫؍‬ 0.1155), 75% and 44% (p ‫؍‬ 0.0016), 70% and 42% (p ‫؍‬ 0.0002), and 87% and 58% (p ‫؍‬ 0.0003) for the MAID and control patient groups, respectively. Acute hematologic toxicity in the MAID group included febrile neutropenia in 12 patients (25%). Wound healing complications occurred in 14 (29%) of 48 MAID patients. One MAID patient developed late fatal myelodysplasia. Conclusion: After aggressive chemoradiation and surgery, these patients showed a significant reduction in distant metastases, with a highly significant gain in disease-free and overall survival compared with a historical control group. On the basis of this experience, the Radiation Therapy Oncology Group conducted a multi-institutional trial.

To examine the prognostic significance, in patients with ovarian cancer, of normalization of CA125 levels in serum during neoadjuvant chemotherapy treatment combined with delayed primary surgical debulking. We carried out a retrospective chart review to identify ovarian cancer patients treated between 1997 and 2005 with neoadjuvant chemotherapy and delayed surgical debulking. Serum levels of CA125 were measured at baseline, prior to each cycle of chemotherapy, and before surgery. &quot;CA125 normalization&quot; was defined as a reduction in serum CA125 levels, in patients with elevated levels at diagnosis, to less than 35 kU/L. Cox proportional hazard models were built to model progression-free survival and overall survival. Ninety patients met the inclusion criteria. Sixteen patients (17.8%) had CA125 normalization before surgery, and 52 patients (57.8%) had normalization at the conclusion of all primary chemotherapy. Cox regression showed that CA125 normalization from neoadjuvant ...