First Site Of Progression Research Articles

Pelvic radiation therapy combined with hepatic artery chemotherapy for resected rectal carcinoma with liver metastases

Purpose : Patients with hepatic metastases from rectal cancer treated with hepatic artery (HA) chemotherapy have a life expectancy great enough to be at risk for pelvic failure. Thererfore, a treatment plans was developed for patients with resected rectal cancer and unresectable hepatic metastases, when the pathologic of concurrent pelvic radiation therapy (RT) and HA 5-fluorouracil (FUra), as systemic levels of FUra are achievable with HA administration, followed by HA fluorodeoxyuridine (FdUrd). Methods and Materials : Fifteen patients were offered combined pelvic RT and HA FUra. Radiation was given to an initial dose of 45 Gy to the pelvis, followed by boost treatment for an additional 5.4–10.8 Gy. Concurrent HA chemotherapy was given using FUra or FUra/leucovorin administered in two cycles of 14 days for each cycle. If HA chemotherapy could not be done, then intravenous FUra was given during RT. Following completion of RT and HA FUra, patients were evaluated for treatment with HA FdUrd. Results : Eleven patients received concurrent HA FUra or FUra/leucovorin and pelvic RT. Of these, six continued to receive HA FdUrd after completion of RT, as five patients were found to have progressive hepatic disease. Four patients could not have therapy as outlined, but did receive pelvic RT with concurrent intravenous FUra (two patients), FUra/leucovorin (one patient), or sequential HA FUra (one patient). There were four pelvic recurrences at 1, 4, 14, and 17 months after RT. One was the first site of progression, two occurred simultaneously with other failure, and one occurred after hepatic progression. The liver was the most frequent site of first progression (alone in seven patients; as a component of progression in four patients). Treatment was well tolerated with three Grade ⩾3 toxicities. The median survival was 14 months. Conclusions : These data support the hypothesis that patients with metastatic rectal cancer are also at risk for pelvic recurrence. The frequency of hepatic progression supports continued aggressive therapy directed to this site. As systemic and regional therapy of metastatic rectal cancer improves, we anticipate that more patients will be at risk for a pelvic recurrence, making it increasingly important to explore the role of pelvic radiation therapy despite the presence of metastatic disease.

Small cell lung cancer: The influence of dose and treatment volume on outcome

The treatment of small cell lung cancer is clearly enhanced by the addition of radiation therapy. Survival increases modestly while local thoracic failure as first site of progression is reduced from approximately 60% when chemotherapy alone is used to 30% after combined modality therapy. The variables of radiation dose and treatment volume seem to be important in the successful management of this disease. Local chest control appears to increase as doses are escalated from low levels (25 Gy) to moderate levels (45 to 50 Gy). With about one third of patients experiencing local chest progression, one can speculate that higher radiation doses might be of value. However, at this time there is no proof that increased dose or dose intensity bears out this promise. Indeed, increasing dose intensity of radiotherapy, eg, twice-daily treatment, increases esophagitis, perhaps reduces local failure, but has not improved overall survival. Using larger total doses or altered fraction schemes must still be considered to be under investigation. To increase dose in a safe manner, reduction in the volume covered by radiation portals will likely need to take place. Modern trials suggest that prophylactic treatment of the radiographically or clinically negative contralateral hilum and/or supraclavicular nodal regions may not be necessary for survival or local control. Importantly, reducing treatment volumes may permit increasing doses without exceding normal tissue tolerance. Also, reduced volumes pave the way for further clinical trials that improve radiation dose delivery by better target definition and more conformal therapy.

The Rationale for EN Bloc Pelvic Lymph Node Dissection for Bladder Cancer Patients with Nodal Metastases: Long-Term Results

From August 1971 through June 1989, 591 consecutive patients underwent curative pelvic lymphadenectomy with en bloc radical cystectomy for bladder cancer. Of these patients 132 (22%) had pathologically proved nodal metastases. The incidence of positive nodes increased with increasing pathological stage of the primary tumor: stage PIS (0.75%), stage P1(13%), stage P2 (20%), stage P3a (24%), stage P3b (42%) and stage P4 (45%). The median followup for the 31 patients still alive was 5.5 years (range 2.6 to 18.8).Recurrent bladder cancer was documented in 89 patients (67%) with a median interval to progression of 1.5 years. Pelvic recurrence as the first site of progression was uncommon, occurring in 15 patients (11%). The actuarial 2, 3, 5 and 10-year survival rates were 55%, 38%, 29% and 20%, respectively. Increased risk of progression and death was associated with advanced pathological tumor stage (stage P3b or greater, p <0.001 and p <0.001, respectively) and 6 or more positive nodes (p <0.001 and p = 0.012, respectively). There was no significant difference in survival and interval to progression among patients who received preoperative irradiation or adjuvant chemotherapy compared to those treated with surgery alone. This retrospective analysis further substantiates the philosophy that single stage pelvic lymphadenectomy with en bloc radical cystectomy can provide long-term progression-free survival, particularly for patients with localized primary tumors and minimal metastatic nodal disease.