Role Of Neoadjuvant Therapy Research Articles

What is the optimal neo-adjuvant treatment for liver metastasis?

Colorectal cancer is the third most common cancer in the Western population and has a 5-year overall survival of 5-10% when metastatic. Approximately 30% of the patients with metastatic colorectal cancer have limited disease apparently isolated to the liver and, if this can be resected, the 5-year overall survival is improved to 30-60%. Therefore, it is important to identify patients who have both resectable disease and those with initially unresectable tumors who can potentially be downsized with chemotherapy to allow resection. First-line doublet chemotherapy regimens lead to response rates of 50-60%, triplet chemotherapy regimens may result in a response rate of up to 70%, and biological agents may add to responses or induce morphologic changes that facilitate disease resection. Surgical advances in recent years have also increased resectability rates and have challenged prior rules of resectability. Local therapies including ablation and radiation, often performed in conjunction with resection, may further aid in control of disease. The aim of this article is to focus on the role of neoadjuvant therapy in the treatment of colorectal liver metastases.

Is neoadjuvant therapy beneficial in clinically staged T2N0 esophageal cancer?

135 Background: The optimal treatment strategy for clinical stage T2N0 (cT2N0) esophageal cancer is poorly defined. The specific aims of this analysis were to determine the impact of neoadjuvant therapy (NAT) in cT2N0 esophageal cancer patients on overall survival, nodal metastasis, staging, and pathological complete responders (pCR) NAT. Methods: We reviewed a retrospective cohort of 27 patients with cT2N0 esophageal cancer at Oregon Health & Science University, an NCI-Designated Cancer Center from 1999 to 2011. All patients were staged pre-operatively using Endoscopic Ultrasound (EUS), CT +/- FDG-PET. Patients were identified into two cohorts: NAT followed by surgery and surgery alone. We compared overall survival between the cohorts using Kaplan-Meier analysis. Results: Eleven patients (41%) received NAT followed by surgery and sixteen patients (59%) underwent surgery alone. Minimal invasive esophagectomy and decreased length of stay (p < 0.05) were associated with the presence of neoadjuvant therapy. The difference in overall survival rate was not statistically significant between NAT and surgery alone groups (p = 0.96). Three of 11 patients (27%) had a pCR and 8 (73%) were partial or non responders after NAT. In the surgery only group, nine of 16 patients (56%) were understaged, 6 (38%) were overstaged and 1 (6%) was correctly staged. Despite being clinically node negative, 14/27 (52%) had node positive disease in both groups with 5/11 (45%) in NAT group and 9/16 (56%) in surgery group. Conclusions: The benefit of NAT in cT2N0 esophageal cancer patients remains unclear. However, our finding of significant clinical understaging and frequent positive nodes in clinically node negative patients suggests a clinical benefit to NAT for some cT2N0 patients before surgery. These observations support design of a prospective clinical trial to define the role of NAT in patients with cT2N0 esophageal cancer.

Role of neoadjuvant therapy and adjuvant therapy in treatment of pancreatic cancer

Role of neoadjuvant therapy and adjuvant therapy in treatment of pancreatic cancer

Últimos avances en tumores de páncreas

Últimos avances en tumores de páncreas

Su1524 Response to Neoadjuvant Therapy and the Lymph Node Ratio (Lnr) are the Strongest Prognostic Factors After Esophageal Resection for Cancer

Su1524 Response to Neoadjuvant Therapy and the Lymph Node Ratio (Lnr) are the Strongest Prognostic Factors After Esophageal Resection for Cancer

Su1525 Surgical and Endoscopic Treatments for Achalasia: A Single Institution Comparison of 190 Patients

Su1525 Surgical and Endoscopic Treatments for Achalasia: A Single Institution Comparison of 190 Patients

Using neoadjuvant therapy for breast cancer in clinical practice: when and how?

The roles of neoadjuvant therapy both as a standard thera-peutic approach and a research tool are very closely tied andhave yielded insights into both breast cancer biology andnew drug development [1, 2]. From a clinician’s standpoint,however, the key questions that arise revolve around theclinical advantages of neo-adjuvant therapy in terms ofsurgical outcomes, long-term recurrence/mortality anddecision-making. At the current time, the main advantage ofneoadjuvant therapy is to improve the odds of adequatesurgical resection, particularly breast-conserving surgery[3, 4]. Beyond that, long-term outcomes or clinical deci-sion-making do not appear to be affected by the sequence ofsystemic therapy in relation to definitive surgery. It isbecoming clear that breast cancer is heterogeneous. Ge-nomically defined subsets, which map to some extent withhormone and HER2 receptor subtypes, exhibit differentialrecurrence hazard reductions with systemic therapies—andthis concept also applies to neoadjuvant therapy response aswell [5]. But there is also clinical diversity, for example,contrasting rapid onset inflammatory cancer to a moreindolent cancer that has been clinically present for severalyears. Therefore, current neoadjuvant treatment paradigmsmust incorporate the base of evidence from large scaleclinical trials as well as the biological context of the disease.The reports contained in this special issue of Breast CancerResearch and Treatment highlight current trends and resultsthat are shaping both patient care and research in this area.The report by Lin et al.[6] demonstrate biological dif-ferences between interval and screen-detected cancerstreated on a prospective trial, even though the number ofscreening-detected cancers was small, as would be typicalin a neoadjuvant trial where the majority of patients werenot undergoing screening. As expected, interval cancershad a tendency to be hormone receptor-negative and ofhigher grade, whereas screen-detected cancers were all ofthe luminal intrinsic subtypes by gene expression array.Nevertheless, this report points to the need to stratifypatients by known characteristics associated with responsein clinical trials and to use established factors in routineclinical practice. For example, it is now clear that patientswith hormone receptor-positive cancer have less responseto neoadjuvant therapy and lower pathologic completeresponse (pCR) rates. Receptor status might thereforeaffect the decision regarding the timing of chemotherapy,especially if breast-conserving surgery is driving thedecision. Several phenotypes that are also related to hor-mone receptor content, but appear to have independentprognostic factors for response, such as proliferation indexand risk score by gene profile assays are the next markerson the horizon that could enter into this decision-making iftumor size reduction is a main goal of therapy [7, 8].Is there an optimum neoadjuvant regimen? Should non-standard adjuvant regimens that yield high pCR rates beadopted into routine practice? Until neoadjuvant trials arepowered for long-term outcome, at the current time, it isimportant to remember that the most important benefit ofneoadjuvant therapy is its ‘‘adjuvant’’ effect on long-termrecurrence and mortality. Therefore, an evidence-basedapproach would dictate the use of proven standard adjuvantregimens in the neoadjuvant setting. However, trials thatbridge pCR rates in relevant subsets to long-term outcomecould serve as the basis for approvals of new drugs andregimens and eventually shorten regulatory approval times[9]. Some long-standing standards may need to be

The role of neoadjuvant chemotherapy in children with malignant solid tumors

The role of neoadjuvant chemotherapy in children with malignant solid tumors

Preoperative Radiation Therapy for Upper Rectal CancerT3,T4/Nx: Selectivity Essential

Preoperative Radiation Therapy for Upper Rectal CancerT3,T4/Nx: Selectivity Essential

Aktueller Stand der neoadjuvanten Therapie bei Weichteilsarkomen

The treatment of soft tissue sarcoma is clinically challenging. Referral to an experienced center with an interdisciplinary team is strongly recommended. Neoadjuvant therapy, including irradiation and chemotherapy, has been applied to improve local control rates, eradicate micrometastases and assess chemosensitivity. However, the role of neoadjuvant therapy remains controversial, especially for systemic therapy, as the only available randomized trial failed to prove a benefit for survival. Nevertheless, on the basis of the current body of literature, neoadjuvant therapy can be considered on an individual basis for patients with high-risk tumors. Whenever possible, patients should be included in a clinical trial.

Therapy of locally advanced pancreatic adenocarcinoma: unresectable and borderline patients

Systemic chemotherapy for advanced pancreatic cancer is commonly used in practice; however, the optimal strategy for both neoadjuvant and adjuvant therapy in this disease remains controversial. A particular challenge remains in patients who are considered to be locally advanced and either unresectable or borderline resectable. Offering optimal neoadjuvant therapy to this group of patients may give them the opportunity to have a curative surgical approach. This article will discuss the potential role of neoadjuvant therapy in borderline, potentially resectable pancreatic cancer. It will also discuss areas of interest in potential targets as the biology of pancreatic adenocarcinoma is further explored.

Adjuvant therapy for pancreas adenocarcinoma: where are we going?

Evaluation of: Neoptolemos JP, Stocken DD, Bassi C et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs. gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304(10), 1073–1081 (2010).Over the last decade, adjuvant therapy in the treatment of resected pancreas adenocarcinoma has had its value established. Such treatment incrementally increases 5-year survivorship and delays time to tumor recurrence. The backbone of adjuvant therapy is the single-agent gemcitabine, based primarily on results from the Charité Onkologie Clinical (CONKO)-001 study. Based on the combined results of the European Study Group for Pancreas Cancer (ESPAC)-1 and ESPAC-3 trials, Neoptolemos and colleagues have established both bolus 5-fluorouracil and leucovorin and gemcitabine as standard options for resected pancreatic cancer. Gemcitabine remains the main standard therapy based on its ease of administration and a more favorable toxicity profile; however, there is now a clearly validated alternate option of 5-fluororuacil and leucovorin based on the results of ESPAC-3. Moving forward, the integration of novel cytotoxic and targeted agents into adjuvant therapy, along with refining the role of neoadjuvant therapy for patients with resectable pancreas cancer, will hopefully accrue a more substantial improvement in outcome for patients with resected pancreas adenocarcinoma.

Neoadjuvant therapy for adenocarcinomas of the duodenum and ampulla of Vater.

279 Background: Adenocarcinomas of the ampulla of Vater and duodenum are both rare periampullary tumors with limited data regarding the use of neoadjuvant therapy. We sought to better define the role of neoadjuvant therapy as compared to adjuvant therapy in patients with high-risk disease. Methods: Retrospective review of the M. D. Anderson Cancer Center (MDACC) tumor registry from 5/1990 to 1/2009 identified 66 cases of ampullary (26 neoadjuvant, 40 adjuvant) and 41 cases of duodenal adenocarcinoma (18 neoadjuvant, 23 adjuvant). Only patients who received adjuvant or neoadjuvant therapy and underwent surgical resection at MDACC where included. High-risk factors were defined as T3 or T4, poor differentiation, or lymph node involvement. Relapse-free survival (RFS) and overall survival (OS) were calculated from the start of surgical resection. Results: Median age was 61 yrs (range 30-82) and 39% were female. Neoadjuvant (n=44) and adjuvant therapy (n=63) consisted of 5-FU chemoradiation in 93% and 65%, systemic 5-FU based chemotherapy only in 5% and 24%, and gemcitabine or irinotecan based therapy in 2% and 11%, respectively. Pathological high-risk factors were seen in 77% and 95% of neoadjuvant and adjuvant patients, respectively. Indications for neoadjuvant therapy were high risk disease (70%), poor surgical candidate (16%), and concern for possible metastatic disease (14%). In the neoadjuvant group T and N downstaging were observed in 25% and 32% of patients, respectively; 3 patients (7%) had a pathological complete response. Neoadjuvant as compared to adjuvant therapy had similar 5-year OS (66% vs. 59%, p =0.8) and 5-year RFS (54% vs. 59%, p=0.4). Variables significant (p <0.05) in the multivariate analysis for OS were age >60 yrs, lymph node involvement, and margin positivity; and for RFS were lymph node involvement and margin positivity. Neither tumor type (duodenal vs. ampullary; OS HR: 1.6, p =0.2; RFS HR: 0.9, p=0.8) nor treatment type (neoadjuvant vs. adjuvant; OS HR: 1.2, p =0.6; RFS HR: 1.1, p=0.7) were significant for OS or RFS in the multivariate model. Conclusions: Neoadjuvant therapy appears to be a viable approach for high-risk duodenal and ampullary adenocarcinomas. Further investigation of this treatment approach is needed. [Table: see text]

Cancer du rein métastatique : bilan préthérapeutique, instauration et suivi d’un traitement anti-angiogénique. À propos d’un cas

Cancer du rein métastatique : bilan préthérapeutique, instauration et suivi d’un traitement anti-angiogénique. À propos d’un cas

The Role of Neoadjuvant Therapy in Sphincter-Saving Surgery for Mid and Distal Rectal Cancer

ABSTRACTCurrent treatment of mid and lower rectal cancer includes neoadjuvant therapy, such as radiotherapy or radiochemotherapy. Randomized trials have demonstrated that neoadjuvant therapy improves local control. However, with the exception of one study, it does not improve overall and cancer-specific survival. In addition, the role of neoadjuvant therapy in enhancing the surgeon’s ability to perform sphincter-saving surgery is still controversial.We provide an overview of reported randomized trials using neoadjuvant therapy in patients with rectal cancer. We have examined the most significant factors influencing sphincter preservation and the manner in which these factors are affected by neoadjuvant treatment.

Oesophagectomy for tumours and dysplasia of the oesophagus and gastro‐oesophageal junction

Neoadjuvant therapy, radical lymphadenectomy and treatment in high-volume centres have been proposed to improve outcomes for resectable oesophageal tumours. The aim of the present study was to review the oesophagectomy experience of a single surgeon with a moderate caseload who uses neoadjuvant therapy selectively and performs a conservative lymphadenectomy. A retrospective review of prospectively collected data was performed. The study included 125 consecutive attempted oesophageal resections performed by a single surgeon (RC) from 1993 to 2006. All patients were staged with computed tomography and also laparoscopy for lower third and junctional tumours. Endoscopic ultrasound was used in 69%. Seventy-seven per cent were adenocarcinomas. Neoadjuvant therapy was used selectively in 23%. One hundred and twenty-one resections were carried out, giving an overall resection rate of 97% with an R0 resection in 82%. In-hospital mortality was 0.8%, clinical anastomotic leak 1.7% and median length of stay 14 days. Overall median and 5-year survival were 46 months and 47%. Stage-specific 5-year survival was 100%, 71%, 41% and 21% for stages 0, I, II and III, respectively. Isolated local recurrence occurred in 8%. A moderate volume surgeon with specialist training in oesophageal resectional surgery can achieve a low mortality and anastomotic leak rate with good survival outcomes. The role for neoadjuvant therapy and radical lymphadenectomy is controversial and remains to be clearly defined. Accurate preoperative staging is essential for selection of patients for curative surgery with or without neoadjuvant therapy and for comparison of results.

Effects of neoadjuvant radiochemotherapy on pathological staging and prognosis for locally advanced esophageal squamous cell carcinoma

The role of neoadjuvant therapy in the treatment of locally advanced esophageal carcinoma still remains controversial. The aim of this study was to evaluate the effects of neoadjuvant radiochemotherapy on pathological staging and prognosis in the patients with locally advanced esophageal squamous cell carcinoma. Between January 1991 and December 2000, 473 patients with advanced esophageal carcinoma diagnosed by endoscopic biopsy underwent surgical resection in our center. With informed consent, they were randomized into four groups: neoadjuvant chemotherapy, neoadjuvant radiotherapy, neoadjuvant radiochemotherapy, and surgery alone (control group). The preoperative computed tomography staging criteria were the following: Stage I, the tumor limited to the esophageal lumen or the thickness of the esophageal wall varied between 3-5 mm; Stage II, the thickness exceeds 5 mm but no invasion to the mediastinum or distant metastasis; Stage III, the tumor invades adjacent mediastinal structure; and Stage IV, there is distant metastasis. The tumor resection rate, pathological stage, treatment-related complication, and survival among groups were compared. The radical resection rate for the patients in radiotherapy and radiochemotherapy groups was increased in comparison with the control group (P < 0.05). Their pathological stage after esophagectomy was regressed significantly than that of the control group (50.85%, 55.08% vs. 0%, P < 0.05). The adjuvant chemotherapy group did show significant improvement on resection rate and pathological staging compared with the control group. The treatment-related complication in the three neoadjuvant groups had no significant difference from that of the control group (P > 0.05). The 3-year survival rate of radiotherapy and radiochemotherapy groups were significantly higher than that of the control group (69.49%, 73.73% vs. 53.38%, P < 0.05). The 5-year survival rate of radiochemotherapy group was higher than that of the radiotherapy group although did not show a statistical difference (P > 0.05). Rational application of neoadjuvant radiochemotherapy seems to provide a modest benefit in radical resection and survival in patients with locally advanced esophageal carcinoma.

Management of retinoblastoma with proximal optic nerve enhancement on MRI at diagnosis

In North America, retinoblastoma rarely presents with gross clinical evidence of tumor involving the optic nerve. Extent of microscopic tumor infiltration into the postlaminar optic nerve is a significant risk factor for metastasis, especially if there is tumor at the cut end. Due to poor outcomes in patients with metastatic disease, historical treatment for patients with clinical evidence of extraocular optic nerve involvement has included upfront enucleation followed by aggressive adjuvant chemotherapy. Additional orbital irradiation is advocated for individuals with optic nerve involvement at the surgical margin. Little is known about the role of neoadjuvant therapy in the setting of orbital optic nerve enhancement on magnetic resonance imaging (MRI) at diagnosis. A retrospective review of consecutive retinoblastoma cases at Childrens Hospital Los Angeles over a 3-year period (2004-2006) found to have gadolinium contrast enhancement in the proximal portion of optic nerve on MRI at diagnosis. Nine patients fit the inclusion criteria. Two had secondary glaucoma of a sufficient degree to cause an enlarged eye (buphthalmos). Median age at presentation was 17 months (2-36 months). All patients received neoadjuvant chemotherapy prior to enucleation. Only two received external beam radiation. All are disease-free with a median follow-up of 22 months (12-41 months). Neoadjuvant chemotherapy is well tolerated prior to enucleation of retinoblastoma-containing eyes associated with contrast enhancement of the proximal optic nerve on MRI at diagnosis. Such an approach may be used to decrease intensity or duration of chemotherapy and need for external beam radiation.

Neo-Adjuvant Hormonal Therapy

Neo-adjuvant endocrine therapy has opened new alternatives for locally advanced breast cancer. Such therapy, which has permitted us to expand the treatment role of neo-adjuvant therapies, may be of great benefit to patient groups such as the elderly, those not suited for chemotherapy, and those whose response may not be optimal. This therapy also may be able to help us identify agents that could improve outcomes in the adjuvant setting as well as possible biologic predictors for outcome. The latest generation of endocrine therapy for breast cancer, aromatase inhibitors, has proved superior to tamoxifen in terms of toxicity and efficacy in the adjuvant setting and is currently being studied in other clinical trials. Current findings indicate that these agents are less toxic and better tolerated than neo-adjuvant chemotherapy and that third-generation anti-hormonal therapy offers improved tumor response compared with tamoxifen, which has resulted in increased breast conserving surgery. Biomarker findings of improved response in tumors that are both estrogen receptor positive and HER-2 positive as well as progesterone receptor positivity only will be important for planning future selective treatment and clinical trials.

Outcome and patterns of recurrence of nonbilharzial pure squamous cell carcinoma of the bladder

Nonbilharzial squamous cell carcinoma (SCC) of the bladder is a rare entity in the Western hemisphere. To further understanding of its natural history, a contemporary experience with management and outcome of this disease was reviewed. Between 1988 and 2003, 27 patients with pure SCC were treated at the center. Charts were reviewed to assess impact of therapy on survival and patterns of recurrence in those that died of disease. The 2-year overall survival and recurrence-free survival (RFS) rates were 47.6% and 32.8%, respectively, with a median follow-up of 15.3 months in survivors. Eight patients received initial chemotherapy and/or radiation therapy with the intent of performing surgical consolidation. In 5 of these patients surgical consolidation was not performed due to rapid progression of disease and death. Of the 3 patients who were treated with neoadjuvant therapy (1 with chemotherapy, 1 with radiation, and 1 with chemoradiation) and had surgical consolidation, 2 (67%) were downstaged at cystectomy and remain disease-free. In 10 of 20 patients who underwent radical cystectomy the disease recurred after a median duration of 5.1 months and 7 died: 3 of local recurrence, 1 of distant recurrence, and 3 of both. History of superficial transitional cell carcinoma that differentiated into pure SCC (P = .035; hazards ratio [HR] of 3.73) and treatment by radical cystectomy (P = .002; HR of 0.19) were associated with RFS. In select patients with resectable disease, radical cystectomy remains the mainstay of therapy for pure SCC of the bladder. Locoregional recurrence is the primary cause of death in the majority of patients. The role for neoadjuvant therapy is unclear.