Died Of Disease Research Articles

Long-term follow-up (>20 years) for one of the original randomized prospective trials evaluating adjuvant chemotherapy in patients with high-grade operable osteosarcoma

10514 Background: Neoadjuvant and adjuvant chemotherapy is now standard practice for patients who present with localized osteosarcoma. We present the long-term follow-up (>20years) for one of the original prospective randomized trials that compared adjuvant chemotherapy to no treatment in patients with high-grade operable osteosarcoma. Methods: The original study was performed at UCLA from 1981 to 1984. During this time, 59 patients with high-grade, operable, non-metastatic osteosarcoma were randomized to receive adjuvant chemotherapy (MSKCC T-10B protocol)(N=32; 24 men, 8 women, median age 15 yrs) vs. expectant management (N=27; 20 men, 7 women, median age 18 yrs). All patients received one neoadjuvant course of intra-arterial doxorubicin hydrochloride (90mg) and radiation (1750cGy). At a median follow-up of 2 years, there was a statistically significant improvement in both disease-free (55% vs. 20%, p<.01) and overall survival (80% vs. 48%, p<.01) for those who received immediate adjuvant chemotherapy. Upon recurrence, patients in the T-10B arm received salvage chemotherapy with doxorubicin hydrochloride and cisplatin while those in the expectant arm received the T-10B protocol. 27 years after the initiation of the trial, long-term follow-up was obtained on all patients. Results: Median follow-up time for survivors was 24 years. 18 patients in the adjuvant chemotherapy arm died of disease (DOD) while 14 have no evidence of disease (NED). 22 patients in the control arm DOD, 1 died of other causes and 4 have NED. The 5, 10, and 20 year disease specific survival (DSS) for the treatment arm (47%, 43%, 43% respectfully) was significantly better than that of the control arm (30%, 26%, 17% respectfully) (p=0.0254). Conclusions: Early administration of chemotherapy in patients with high-grade operable osteosarcoma provides a significant survival benefit that is maintained with long-term (>20 years) follow-up. These results support the idea that early systemic treatment offers the best opportunity to cure patients with this high-risk malignancy. No significant financial relationships to disclose.

Salvage Surgery for Recurrent Nasopharyngeal Carcinoma

To present our experience of salvage surgery for recurrent nasopharyngeal carcinoma after primary treatment by radiotherapy. Eleven of 25 patient treated for nasopharyngeal carcinoma between 1990 and 2003 with radiotherapy had either residual or recurrent disease and underwent salvage surgery. The type C infratemporal fossa approach was used to access residual tumor. The patients' progress was followed by clinical examination and interval magnetic resonance scans. The results were analyzed in terms of morbidity and oncological outcome; patients were recorded as NED (no existing disease), AWD (alive with disease), and DOD (died of disease). A disease-free survival rate of 72% was achieved in the salvage surgery group of patients and an overall disease-free survival rate of 56% applied to the initial cohort of 25 patients, following both the single mode and combined treatment. Salvage surgery is feasible for patients with recurrent nasopharyngeal carcinoma and may be achieved with minimal morbidity using the type C infratemporal fossa approach.

The treatment of lateral T1 and T2 squamous cell carcinomas of the vulva confined to the labium majus or minus

To determine the pattern of lymph node metastases, recurrence rate, and survival of patients with lateral T1 and T2 squamous cell cancer (SCC) of the vulva treated by radical vulvectomy or hemivulvectomy and inguinal lymphadenectomy. An institutional review was performed to identify lateral T1 and T2 SCC of the vulva confined to the labium majus and minus. Sixty-one patients with lateral T1 and 61 patients with lateral T2 SCC of the vulva were treated from 1963 to 2003. Radical vulvectomy (RV) was performed in 60 patients, and radical hemivulvectomy (RHV) in 62 patients. Seven of 61 patients (11%) with T1 lesions had ipsilateral superficial inguinal lymph node (SIL) metastases, but none had deep inguinal lymph (DIL) node metastases. Nineteen of 61 patients (31%) with T2 lesions had ipsilateral SIL metastases, and 8 had ipsilateral DIL metastases. No patient had contralateral SIL or DIL metastases. Six patients (10%) with T1 lesions and seven patients (11%) with T2 lesions developed recurrence to the ipsilateral vulva and were treated by re-excision. All patients are alive with no evidence of disease 10-195 months after treatment. One patient with T1 and three patients with T2 SCC developed distant recurrence and died of disease (DOD) 10-15 months after surgery. Disease-free survival of patients with T1 lesions was 98% at 2 years and 98% at 5 years, and with T2 lesions was 95% at 2 years and 93% at 5 years. Local or distant recurrence was not more common in patients treated by RHV than in those treated by RV. Lateral T1 and T2 squamous cell cancers of the vulva spread to the ipsilateral inguinal lymph nodes and can be treated effectively with RHV and ipsilateral SIL dissection. Deep inguinal lymphadenectomy is indicated only when the SIL are positive.

Indication for neoadjuvant chemotherapy in adult patients with high-risk soft-tissue sarcomas

9578 Background: To determine the efficacy and safety of neoadjuvant chemotherapy for local tumour control and overall survival in patients with high-risk soft-tissue sarcomas (tumour size ≥ 5 cm, G II/III, extracompartimental and deep localisation) we have analyzed the clinical outcome in 25 patients. Methods: Patients with high-risk soft-tissue sarcomas were treated with four cycles of etoposide 125 mg/m2/day 1+4, ifosfamide 1500 mg/m2/day 1–4 and doxorubicin 50 mg/m2/day 1 (EIA regimen) followed by definitive surgery with or without postoperative radiotherapy and adjuvant chemotherapy. 21 patients received chemotherapy in a combined neoadjuvant/adjuvant clinical setting; eighteen of them completed adjuvant chemotherapy. Four patients received chemotherapy in an adjuvant setting only. Results: The objective response rate of neoadjuvant chemotherapy assessable in 21 patients was 43%. Including NED (n = 7) and partial remissions (n = 3), the radiographic response rate was 47.6% with additional 42.9% stable diseases (n = 9). Surgery was performed in two patients before completing the four neoadjuvant chemotherapy cycles because of disease progression. Median overall survival for all patients from the time of first diagnosis was 21.6+ months [range: 8 - 50] and from the start of treatment 20.5+ months [range: 8 - 49]; median progression-free survival after start of treatment was 18.6+ months [range: 1 - 49]. After completion of chemotherapy, R0-resection could be performed in 13 of 21 patients (60%). At completion of entire treatment, 21 of 25 patients (84%) had NED after R0- and R1-resection. Two patients showed no disease progression after R2-resection and are alive with disease (AWD) 21 and 18 months after start of treatment. Two patients died of disease (DOD) ten and eight months after first diagnosis due to metastases. Conclusions: The high proportion of R0-resections supports the idea of a tumour downstaging after neoadjuvant treatment. Our data support the hypothesis that neoadjuvant chemotherapy might be beneficial as an integral part in the treatment strategy of high-risk soft-tissue sarcoma patients. No significant financial relationships to disclose.

Adjuvant whole abdominal irradiation in clinical stages I and II papillary serous or clear cell carcinoma of the endometrium: A phase II study of the Gynecologic Oncology Group

Objectives. To evaluate outcome in patients with clinical stage I/II papillary serous (PS) or clear cell (CC) endometrial carcinoma treated with whole abdominal radiotherapy. Methods. After total abdominal hysterectomy with bilateral salpingo-oophorectomy, pelvic/para-aortic lymph node sampling, and peritoneal washings, eligible patients received radiotherapy (RT) to the abdomen (3000 cGy at 150 cGy/day) with a pelvic boost (1980 cGy at 180 cGy/day). Results. Among 21 PS patients (median age: 68 years), one refused therapy, and another received a non-protocol vaginal boost. In total, eight patients died of disease (DOD) between 9.6 and 35.2 months. Five others died due to protocol treatment (1), toxicity from subsequent chemotherapy (1), intercurrent disease (1), and unknown cause (2). Five-year progression-free survival (PFS) was 38%. Among treated patients who DOD, sites of recurrence included lung (2), lung/vagina (1), abdomen/pelvis (1), vagina (1), and abdomen (2). Among 13 CC patients (median age: 63 years), one received pelvic RT only and died with intercurrent disease. Five others died due to DOD (3), intercurrent disease (1), and unknown cause (1). Five-year PFS was 54%. Among patients who DOD, sites of recurrence included lung (1), vagina (1), and unknown (1). Grade 3/4 toxicities for both histologic groups included gastrointestinal (three grade 4; three grade 3), hematologic (one grade 4), and cutaneous (one grade 3). Conclusions. Over half of the treatment failures were within the radiation field. Systemic chemotherapy, radiosensitizing chemotherapy, or sequential radiation and chemotherapy should be considered in future adjuvant trials for these patients.

Intraoperative extracorporeal irradiation and replantation in local treatment of primary malignant bone tumors

In 13 patients with primary malignant bone tumors (10 Ewing's sarcoma, 1 parosteal osteosarcoma, 1 adamantinoma recurrence, and 1 MFH) local therapy was performed as intraoperative extracorporeal irradiation and replantation (IEIR) of the involved bone segment (5 tibia, 2 femur, and 6 pelvis). Of the 13 patients (69%), 9 are alive at the time of the follow-up (5 CDF, 4 AWM(treated)) and 4 patients died of disease (DOD). Up to now during the follow-up of 32 months (6-57), no local recurrence was observed in the replanted bone segments. The complication rate was very high (18 complications in 11 of the 13 patients, including 6 cases with complication V degrees according to Ruggieri with loss of the reconstruction). The typical complication is severe local infection necessitating removal of the replant. In cases of mechanical failure, the replanted segment could mostly be preserved by surgical revision and autologous bone grafting. If serious complications can be managed or avoided, functional results can be achieved. IEIR must be seen as an extraordinary reconstruction procedure in cases where established procedures such as endoprosthesis, biological reconstructions, or rotationplasties cannot be used or are refused by the patient.

A Clinicopathologic Analysis of Urothelial Carcinomas Diagnosed on Prostate Needle Biopsy

No data exist on urothelial carcinoma diagnosed on prostatic needle biopsy. We reviewed 21 cases (19 consultations) of urothelial carcinoma diagnosed on prostate needle biopsy from 1991 to 1998. In 13 of 21 (62%) cases, urothelial carcinoma showed in situ urothelial carcinoma involving prostatic ducts and acini (DCIS) only; 6 of 21 (29%) cases showed both DCIS and invasive carcinoma and 2 of 21 (9%) cases showed widespread stromal invasion without DCIS. In contrast to prostatic adenocarcinoma, cases exhibited greater nuclear pleomorphism, variably prominent nucleoli, increased mitoses, and necrosis. Immunostains for PSA and PSAP were negative in all 18 cases studied. CK7 was positive in 14 of 16 cases, CK20 was positive in 13 of 16 cases, and 34betaE12 was positive in 11 of 17 cases. A total of 7 of 17 (41%) men had no prior or subsequent history of urothelial carcinoma outside the prostate, 6 of 17 (35%) had concurrent urothelial cell carcinomas of the bladder (1 with extensive carcinoma in situ [CIS] at cystoprostatectomy), 2 of 17 (12%) had a prior urothelial cell carcinoma, and 2 of 17 (12%) developed urothelial cell carcinomas outside the prostate subsequent to the needle biopsy diagnosis. A total of 14 of 18 (78%) men had an elevated prostate specific antigen (PSA), abnormal digital rectal examination, or abnormal ultrasound suggestive of prostatic adenocarcinoma. Follow-up information was available in 17 cases. Six of nine (67%) patients with DCIS eventually died of disease (DOD) (2 with prior urothelial cell carcinoma, 1 with no prior or subsequent history, 3 without information), and 3 of 9 (33%) patients with DCIS were alive with residual disease (AWD). Of the patients with invasive carcinomas, 4 of 8 (50%) were DOD, 2 of 8 (25%) were AWD, and 2 of 8 (25%) were alive without evidence of disease. All men who are alive were treated aggressively with surgery and often adjuvant chemotherapy-radiation. Overall, 10 of 17 (59%) men were DOD with a mean survival after diagnosis of 23.2 months (2-72 months). The diagnosis of urothelial carcinoma on prostate needle biopsy is difficult because it is rare and clinically can mimic prostatic adenocarcinoma; often there is no history of urothelial carcinoma elsewhere. Although the prognosis is poor even with only apparent DCIS, histologic recognition is essential because the only opportunity for improved outcome is early and aggressive treatment.

Erratum

To determine the efficacy of chemotherapy after failed initial treatment in patients with high risk gestational trophoblastic neoplasia (GTN).We performed a retrospective IRB-approved chart review of all patients with GTN seen at a single institution from 1985 to 2015, including all patients who failed initial treatment. We summarized clinical characteristics with descriptive statistics and estimated progression-free survival (PFS) and overall survival (OS) with the Kaplan-Meier method.Of 68 identified patients, 38 required > 2 chemotherapy regimens. Patients were treated for GTN (n = 53), including choriocarcinoma, persistent GTN, and invasive mole; for placental site trophoblastic tumor (PSTT) (n = 5); and for intermediate trophoblastic tumor (ITT) (n = 10). Patients with GTN had a median of 2 salvage regimens, median PFS of 4.0 months, and median OS was not reached at median follow-up of 71.2 months. Active regimens included EMACO, MAC, BEP, platinum- and etoposide-based combination therapies, and ICE; 8 of 53 patients died of disease (DOD). Patients with PSTT had a median of 3 salvage regimens, median PFS of 2.8 months, and median OS of 38.8 months. Active regimens included ICE and EMA-EP; 4 of 5 patients DOD. Patients with ITT had a median of 3 salvage regimens, median PFS of 4.1 months, and median OS of 38.2 months. Active regimens included liposomal doxorubicin, platinum-containing regimens, EMA-CO, and EMA-EP; 7 of 10 patients DOD.Several salvage chemotherapy regimens demonstrate activity in high risk GTN. Multiple regimens may be required and cure is not universal.

Sinonasal undifferentiated carcinoma: A 10-year experience

Purpose: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive malignancy of the paranasal sinuses and nasal cavity. Of the few reported series, most indicate a dismal prognosis. In this report, the clinical presentation, histopathologic criteria used for diagnosis, mode of treatment, and outcome are evaluated in seven patients with SNUC. Materials and Methods: Seven patients with SNUC treated at the University of Cincinnati between 1983 and 1993 were analyzed retrospectively. Results: Most of the patients presented with extensive local disease, and two patients also had cervical metastases. All except one were treated using a multimodality approach. Four of the seven patients died of disease (DOD), with a mean survival of only 11.5 months following treatment. Inability to eradicate local disease was responsible for treatment failure in all cases. Three patients have achieved short-term control of disease following combined therapy, but one is at high risk for recurrence. Conclusion: SNUC was associated with an overall poor prognosis in our series despite aggressive treatment. Control of local disease was the central therapeutic consideration. Intensive multimodality therapy is recommended for all patients with SNUC.

Flow cytometric analysis of cellular DNA content in ovarian cancer

A total of 169 paraffin-embedded tissue sections from 42 patients with epithelial ovarian cancer were subjected to analysis of cellular DNA content by flow cytometry. Twenty-three cases were found to be homogenously diploid, whereas 19 cases were aneuploid. A “mosaic” type containing both aneuploid and diploid cell populations was found in 11 of 19 aneuploid cases. Clinical features showed significant correlation with tumor ploidy of FIGO stage and bulky disease. In evaluation of the prognostic value of tumor ploidy, “mosaic” tumors were frequently observed in women who died of disease (DOD), whereas women with diploid tumors survived longer than those with “mosaic” tumors. The present results suggest that determination of DNA heterogeneity may be a valuable parameter in the prognosis of epithelial ovarian Cancer.

Endocurietherapy in Pediatric Oncology

Endocurietherapy (brachytherapy) is the placing of radioactive sources directly into or near a solid tumor. This technique delivers a concentrated dose of radiation to a restricted volume while minimizing radiation effects on normal tissue. We have treated 11 patients (nine sarcomas, one carcinoma, and one Wilms') with endocurietherapy procedures as part of their multimodality treatment program. Six were treated as part of the primary management, and the other five were treated for recurrent or metastatic disease. Temporary afterloaded implants using ribbons embedded with radioactive iridium192 (Ir192) seeds delivered typical tumor doses of 4,000 cGy. Six patients, including four primary cases and two recurrent cases, are currently classified as no evidence of disease (NED) without further local regional treatment (follow-up of 11-62 months; median, 38 months), and one patient treated for metastasis also remains locally controlled. Two patients are classified as alive with disease (AWD), two died of disease (DOD), and one is now NED after surgical salvage. Special considerations were given to gonadal shielding, radioprotection techniques, and psychosocial issues in this pediatric population.