[show abstract][hide abstract] ABSTRACT: To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer.
Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m(2)/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m(2) weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here.
Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P < .001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P < .001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014).
Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.
Journal of Clinical Oncology 05/2011; 29(20):2773-80. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: The object of neoadjuvant chemoradiotherapy regimens is a downstaging or downsizing of advanced rectal tumor to increase the rate of curative resection and reduce loco-regional failure. A reliable method of assessing response to adjuvant therapies is required to help standardize the assessments of new multimodality therapies. The purpose of this study was to evaluate the role played by tumor regression grading on the evaluation of pathological response to chemoradiotherapy, compared with both the predicting value of the clinical response to neoadjuvant therapy and pathologic response evaluation.
From 1994 to 2003, 58 patients with a primary diagnosis of rectal cancer were studied at our department and enrolled in a single center, not randomized study based on 5-week sessions of radiotherapy associated with a 30-day 5-fluorouracil (FU) infusion, followed by surgical resection. Instrumental restaging and routine histological examination, including tumor regression grading, were performed to asses the response to neoadjuvant therapy.
The cCR rate corresponds to pCR rate, while a 3.5% of cPR and a 3.4% of cSD corresponded to a pPD. cPR and cSD show a PPV of 92.8% and 90.9% respectively, while cPD NPV is 20%. No case was found with no regression (grade 0). Tumor regression was defined grade 1 in 24.5% of cases, grade 2 was found in 58.5% of cases, 7.5% were grade 3, and 9.5% showed complete regression (grade 4). Pathologic response resulted to be associated with regression grade (p=0.006). Tumor regression grading is an independent variable for pT (p=0.0002), pN status (p=0.00004), pathologic staging (p=0.000001) and local recurrence (p=0.003).
Our results lead us to consider only pathologic evaluation to determine the response to neoadjuvant treatment: the application of tumor regression grading on the specimens obtained after combined neoadjuvant chemoradiotherapy and surgery is useful to plan a better therapeutic strategy on the ground of a quantitative evaluation of the response to neoadjuvant treatment; it shows it is an important comparable pathological feature, useful in comparing different protocols' results and differences between patient's response as well as prognostic factors.
International Journal of Colorectal Disease 02/2007; 22(1):7-13. · 2.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: La radio-chemioterapia neoadiuvante (CRT) è un trattamento largamente diffuso e applicato nella cura del cancro del retto. L'as-sociazione di infusione continua di 5-FU e radioterapia loco-regio-nale incrementa la risposta del tumore primitivo alle radiazioni ed elimina le micrometastasi sistemiche con un miglioramento della sopravvivenza complessiva e di quella libera da malattia. Scopo dello studio Lo studio valuta i risultati clinici dei pazienti arruolati presso il nostro Dipartimento di Chirurgia per un protocollo radio-chemiote-rapico associato alla chirurgia per il trattamento del cancro del retto. Metodi Dal novembre 1994 al maggio 2003, presso il nostro dipartimen-to, 58 pazienti affetti da cancro del retto, 35 uomini (60,4%) e 23 donne (39,6%) con una età media di 59,98 ± 10,76 anni (media ± DS), sono stati arruolati in un protocollo di studio di radio-chemio-terapia neoadiuvante seguito da trattamento chirurgico. Lo studio monocentrico, non randomizzato, è consistito in un ciclo di 5 setti-mane di sessioni quotidiane di radioterapia (dose totale 46 Gy) asso-ciato a 30 giorni di infusione continua di 5-FU (300 mg/m 2 /die), al cui termine i pazienti sono stati sottoposti a resezione chirurgica.
[show abstract][hide abstract] ABSTRACT: Multimodality therapy has become the standard treatment for patients with locally advanced (T3 and T4) rectal carcinoma. Accurate preoperative staging of the patients with rectal cancer has increased in importance because the selection of patients with transmural rectal cancer (T3 or T4) or node-positive disease leads to a previous nonsurgical neoadjuvant treatment. The purpose of this study was to evaluate the predictive value of the clinical response to neoadjuvant therapy on the basis of pathological results obtained on rectal cancer patients treated by chemoradiotherapy and surgery.
From 1994 to 2003, 58 patients with a primary diagnosis of rectal cancer were studied at our department and enrolled in a neoadjuvant protocol of chemoradiotherapy followed by surgery. All patients were treated by 30 days of chemoradiotherapy. At the end of the chemoradiotherapy, each patient underwent clinical examination, including digital rectal examination, proctoscopy and abdominal-pelvic computerized tomography to define the clinical response to the chemoradiotherapy. Surgical resection was performed in all patients three weeks after the end of chemoradiotherapy, and histological analysis was performed on all resected specimens.
The clinical complete response rate corresponded to the pathological complete response rate, whereas the clinical evaluation overestimated partial response and stable disease. The pathologic examination revealed that 3.5% of clinical partial responses and 3.4% of clinical stable disease were really pathological progressive disease. Clinical partial response and clinical stable disease positive predictive values were 92.8% and 90.9%, respectively, whereas the clinical progressive disease negative predictive value was 20%. Then, 6.9% of patients believed to have responded to the therapy, or not to have responded or worsened, actually had worsened by the end of the chemoradiotherapy.
Positive and negative predictive values, in particular for partial response and stable disease, of clinical evaluation of the response to chemoradiotherapy were not high enough to consider clinical evaluation accurate enough to make treatment decisions.
[show abstract][hide abstract] ABSTRACT: After brief notes on techniques used to radiate the spine, its indications and the limits of doses required by its adjacency to the spinal cord, our experience in the treatment of 28 patients with a diagnosis of Ewing's sarcoma localized in the spine, not metastatic at onset, that came to our observation between 1980 and 1994 is reported. All of the patients were treated by chemotherapy. As for local treatment radiotherapy was performed in all of the cases, in 50% of cases it was associated with surgery (6 laminectomies, 6 excisions, and 2 vertebrectomies). Five-year survival rate was 43.5%. The prognosis of this group of patients was intermediate among forms localized in the limbs and those localized in the pelvis. There is a greater frequency of cerebral (20%) and skeletal metastases (55%) as compared to the disease that occurred in other sites where secondary pulmonary localizations generally prevailed. Local control was similar for disease occurring in other sites despite the need to deliver doses that were lower than those typically used for this pathology in regions above the cauda.
La Chirurgia degli Organi di Movimento 83(1-2):105-11.