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Combined-modality therapy of esophageal cancer with radiotherapy, etanidazole, and cisplatin-fluorouracil, with or without surgery: neurotoxicity, other toxicities and outcome.

PURPOSE: To investigate whether etanidazole and cisplatin can be given safely together and to evaluate the relationship between incidence of peripheral neuropathy and cumulative exposure to etanidazole and cisplatin, as well as other toxicities and treatment outcome. METHODS AND MATERIALS: Thirty-two previously untreated patients with locally advanced esophageal cancer were entered on a Phase I study of etanidazole combined with radiation therapy and chemotherapy. Cisplatin/5-FU (two cycles, weeks 1 and 4) and etanidazole (weeks 2, 3 and 5) were given concurrently with radiation therapy. Eligible patients then underwent surgical resection. All patients were scheduled to receive two additional cycles of cisplatin/5-FU chemotherapy after completion of radiation therapy (definitive arm) or surgery (preoperative arm). RESULTS: Of 19 fully evaluable patients, nine (47%) developed peripheral neuropathy. Six of six patients, 65 years or older, experienced peripheral neuropathy, compared with three of 13 patients less than 65 years old (p = .003). For patients younger than 65 years, two of the two patients with single dose area under the curve (AUC) > 4.0 mMhr experienced peripheral neuropathy, compared with one of 11 patients with single-dose AUC < 4.0 mMhr (p = .03). Grade 4 toxicity included neutropenia (23%) and thrombocytopenia (26%). No other Grade 4 toxicity was observed. The pathologic complete response rate in patients who underwent surgical resection was 29%. CONCLUSION: This regime of chemotherapy, radiotherapy, and etanidazole had acceptable toxicity. However, combining etanidazole and cisplatin appears to increase the risk of developing peripheral neuropathy for at least some categories of patients. Further studies of these interactions are needed.

Adenocarcinoma

Preoperative infusional chemoradiation therapy for stage T3 rectal cancer.

PURPOSE: To evaluate preoperative infusional chemoradiation for patients with operable rectal cancer. METHODS AND MATERIALS: Preoperative chemoradiation therapy using infusional 5-fluorouracil (5-FU), (300 mg/m2/day) together with daily irradiation (45 Gy/25 fractions/5 weeks) was administered to 77 patients with clinically Stage T3 rectal cancer. Endoscopic ultrasound confirmed the digital rectal exam in 63 patients. Surgery was performed approximately 6 weeks after the completion of chemoradiation therapy and included 25 abdominoperineal resections and 52 anal-sphincter-preserving procedures. RESULTS: Posttreatment tumor stages were T1-2, N0 in 35%, T3 N0 in 25%, and T1-3, N1 in 11%; 29% had no evidence of tumor. Local tumor control after chemoradiation was seen in 96% (74 out of 77); 2 patients had recurrent disease at the anastomosis site and were treated successfully with abdominoperineal resection. Overall, pelvic control was obtained in 99% (76 out of 77). The survival after chemoradiation was higher in patients without node involvement than in those having node involvement (p = n.s.). More patients with pathologic complete responses or only microscopic foci survived than did patients who had gross residual tumor (p = 0.07). The actuarial survival rate was 83% at 3 years; the median follow-up was 27 months, with a range of 3 to 68 months. Acute, perioperative, and late complications were not more numerous or more severe with chemoradiation therapy than with traditional radiation therapy (XRT) alone. CONCLUSIONS: Excellent treatment response allowed two-thirds of the patients to have an anal-sphincter-sparing procedure. Gross residual disease in the resected specimen indicates a poor prognosis, and therapies specifically targeting these patients may improve survival further.

Adenocarcinoma

Sequential cisplatin-doxorubicin, early debulking surgery and intraperitoneal chemotherapy in advanced ovarian cancer. Groupe d'Etude et de Recherche sur les Cancers de l'Ovaire et Digestifs (GERCOD).

40 patients with advanced ovarian cancer were treated with immediate debulking followed by sequential cisplatin and doxorubicin every 4 weeks, followed by second-look laparotomy (SLL). Six courses were given when residual disease (RD) was under 2 cm. When RD was over 2 cm, three courses were followed by early debulking and six more courses before SLL. Immediate debulking was optimal in 15 patients (38%) and early debulking in an additional 15 (38%). Pathological complete responses (34 evaluable cases) were observed in 14 cases (41%), partial response in 13 (38%), stable disease in 3 (9%) and progression in 5 (15%). Toxicity was mainly haematological. 11 patients with negative SLL and 15 with RD under 2 cm received intraperitoneal cisplatin 200 mg/m2 alone or with cytarabine. Median survival was 45 months: 58 months for RD under 2 cm at initial laparotomy and 31 months for RD over 2 cm. Median survival was 46 months when early debulking was successful. 5 year disease-free survival was only 16%. However, this multimodal treatment offers prolonged survival, especially in patients optimally debulked either at initial laparotomy or at early debulking surgery.

Adult

The impact of received dose intensity on the outcome of advanced ovarian cancer.

It has been demonstrated that the prognosis of ovarian cancer is influenced by the dose intensity of cytotoxic treatment. The impact of received dose intensity of platinum-based combination chemotherapy on disease outcome was analysed in 226 stage III-IV ovarian cancer patients entered into two prospective randomised trials. All patients received either cisplatin or carboplatin and cyclophosphamide with or without doxorubicin for six courses after primary surgery. The impact of the received dose intensity of each drug (RDI), the average received dose intensity of the treatment regimen (ARDI) and the relative total drug dose (RTD) on progression-free survival (PFS) and survival were analysed. In the 198 patients receiving the full six courses of treatment, RDI of cisplatin or carboplatin, ARDI and RTD were > 0.76 in 74.2, 61.1 and 65.1% of cases, respectively. Although the differences were not significant, pathological complete response was more frequently observed in the group of patients with ARDI < 0.75, whereas the partial response rate was higher in the ARDI > or = 0.76 group. Median survival and PFS were 19 and 13 months; 22 and 10 months; 23 and 13 months for the groups of patients receiving chemotherapy at a ARDI of < 0.75, > or = 0.76-0.99 and > 1.00, respectively (P = not significant). It appears that modest dose modifications and brief treatment delays during first-line platinum-based chemotherapy do not affect response rate, survival and PFS in advanced ovarian cancer patients.

Antineoplastic Combined Chemotherapy Protocols

Pembrolizumab plus chemotherapy followed by pembrolizumab in participants in Asia with early triple-negative breast cancer: An updated subgroup analysis of the KEYNOTE-522 randomized clinical trial.

BACKGROUND: In KEYNOTE-522 (NCT03036488), addition of perioperative pembrolizumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR), event-free survival (EFS), and overall survival (OS) in early-stage triple-negative breast cancer (TNBC). pCR and EFS results in participants enrolled in Asia were consistent with those in the overall population. We report OS, updated EFS, and safety outcomes in participants enrolled in Asia. METHODS: Participants with newly diagnosed, high-risk, early-stage TNBC (T1c [N1&#x2012;N2] or T2&#x2012;T4 [N0&#x2012;N2] per AJCC 7th edition) were randomized 2:1 to 8 cycles of neoadjuvant pembrolizumab 200&#x202f;mg Q3W or placebo plus chemotherapy. After definitive surgery, participants received adjuvant pembrolizumab 200&#x202f;mg Q3W or placebo for &#x2264;9 cycles. Primary endpoints were pCR (ypT0/Tis ypN0) and EFS. OS was a secondary endpoint. RESULTS: Of 1174 randomized participants, 216 were enrolled in Asia. At data cutoff (March 22, 2024), EFS events occurred in 18/136 participants (13.2%) in the pembrolizumab&#xa0;+&#xa0;chemotherapy group versus 22/80 (27.5%) in the placebo&#xa0;+&#xa0;chemotherapy group (HR, 0.43 [95% CI, 0.23&#x2012;0.81]); 60-month EFS rates (95% CIs) were 87.4% (80.6%&#x2012;92.0%) and 72.1% (60.7%&#x2012;80.6%), respectively. In the respective groups, 12/136 (8.8%) and 16/80 participants (20.0%) died (HR, 0.41 [95% CI, 0.19&#x2012;0.86]); 60-month OS rates (95% CIs) were 91.9% (85.8%&#x2012;95.4%) and 81.1% (70.5%&#x2012;88.1%). Treatment-related AEs led to treatment discontinuation in 19/136 participants (14.0%) with pembrolizumab&#xa0;+&#xa0;chemotherapy and 7/79 (8.9%) with placebo&#xa0;+&#xa0;chemotherapy. CONCLUSIONS: OS and updated EFS outcomes in KEYNOTE-522 participants enrolled in Asia were consistent with those in the overall population and support use of perioperative pembrolizumab&#xa0;+&#xa0;neoadjuvant chemotherapy as a standard-of-care treatment in this setting.

Adjuvant

Prognostic and predictive value of HRD in early triple negative breast cancer (TNBC).

This review explores the emerging role of homologous recombination deficiency (HRD) as both a prognostic and predictive biomarker in early-stage triple-negative breast cancer (TNBC). HRD arises from the defective repair of DNA double-strand breaks through homologous recombination, resulting in genomic instability and increased sensitivity to DNA-damaging agents such as platinum compounds. The review outlines the biological basis of HRD, including genomic signatures such as loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions, and highlights its prevalence in TNBC compared with other breast cancer subtypes. Clinical trials have shown that HRD-positive patients often achieve higher pathological complete response rates and improved disease-free survival when treated with chemotherapy. However, conflicting evidence across trials underscores the need for more reliable and standardized methods for HRD assessment. The review also explores the therapeutic potential of poly(ADP-ribose) polymerase inhibitors in TNBC, particularly in BRCA-mutated or HRD-positive tumors. Agents such as olaparib, talazoparib, and niraparib have demonstrated promising efficacy in both neoadjuvant and adjuvant settings with some trials suggesting that selected patients may avoid chemotherapy. Furthermore, HRD-positive tumors are characterized by increased genomic instability and a higher neoantigen burden, promoting immune cell infiltration, particularly of tumor-infiltrating lymphocytes, which may enhance responsiveness to immune checkpoint inhibitors. Overall, current evidence supports the role of HRD as a promising biomarker in TNBC. However, further research is required to refine its clinical utility and to integrate HRD testing into personalized treatment strategies, especially in combination with emerging therapies such as immunotherapy.

Humans

Preoperative chemoradiation downstages locally advanced ultrasound-staged rectal cancer.

BACKGROUND: This prospective study assessed the effect of preoperative radiation and chemotherapy on the pathologic staging of advanced rectal cancer. METHODS: Twenty patients with rectal cancer were treated with combined chemoradiation prior to operation, after pretreatment staging of all lesions with transrectal ultrasound (TRUS). Perirectal fat invasion served as minimal criteria for preoperative neoadjuvant therapy. The pretreatment stage of these rectal lesions as defined by TRUS was then compared with the pathological stage of the surgical specimen following resection. Cancers were treated with high-dose radiation (45 to 54 Gy) in 19 of 20 patients. One patient received in excess of 60 Gy because of tumor characteristics. Chemotherapy consisted of 5-fluorouracil delivered as a continuous infusion or bolus therapy. Four to 8 weeks after neoadjuvant therapy, 13 abdominal perineal resections, 5 low anterior resections, and 2 completion proctectomies were performed. RESULTS: Following resection, rectal cancer was downstaged in 14 of 20 patients. No tumor was present in the rectal wall in 8 of 20 patients. Complete pathological response was present in 7 of 20 patients. Local recurrence occurred in 2 of 20 patients. Disease-free survival in the remaining 17 of 20 patients ranges from 9 to 51 months (average 26). CONCLUSIONS: Preoperative chemoradiation in the surgical management of advanced rectal cancer results in demonstrable tumor downstaging.

Adult

Cisplatin combined with carboplatin: a new way of intensification of platinum dose in the treatment of advanced ovarian cancer. Belgian Study Group for Ovarian Carcinoma.

We performed a phase I-II trial of escalating doses of cisplatin (CDDP: 50-100 mg/m2 per course) plus carboplatin (CBDCA: 300-400 mg/m2 per course) as a potential way in which to maximize platinum doses without causing excessive toxic effects in patients with advanced ovarian cancer. Thirty-three patients with nonoptimally debulked disease of FIGO (International Federation of Gynecology and Obstetrics) stages IIc-IV [median age: 60 yr; median WHO (World Health Organization) performance status: 2; no prior chemotherapy] received a median of six courses of therapy. CBDCA was infused on day 1 and CDDP on day 2 with an aggressive 48-hour hydration regimen. Myelosuppression was dose-limiting: at the highest dose levels, WHO grade 4 neutropenia and thrombocytopenia led to dose reduction and/or treatment delay in 45% of the patients. Nonhematologic toxic effects included acute nausea and vomiting (97% of the patients), mild alopecia (45%), ototoxic effects (39%), neurotoxic effects (21%), and renal toxic effects (serum creatinine greater than 1.5 mg/dL: 12.5%). The pathologic complete response rate was 22%. We conclude that CBDCA and CDDP can be given safely in combination at reasonably high doses (CBDCA at 300 mg/m2 per course and CDDP at 100 mg/m2 per course) over a 6-month period, provided a close hematologic follow-up is conducted. Randomized clinical trials are needed to define whether this regimen is any better than standard combination chemotherapy.

Adult

A randomized study of sequential versus alternating combination chemotherapy in advanced ovarian carcinoma.

The concept of using either alternating or sequential combination chemotherapy with non-cross-resistant combinations was tested in a randomized trial including 301 previously untreated patients with advanced epithelial ovarian carcinoma. The sequential schedule consisted of CAF (cyclophosphamide, doxorubicin, 5-fluorouracil) followed by PH (cisplatin, hexamethylmelamine) in nonresponders, CAF- greater than PH (n = 157), and the alternating regimen consisted of CAF/PH (n = 144). With a median observation time of 54 months, no statistically significant differences were found between the pathologically complete response (PCR) rates of 17% and 16%, respectively, nor were there any statistical differences in median disease-free survival for PCR patients (CAF- greater than PH 34+ months and CAF/PH 26+ months), in overall survival (28 and 24 months, respectively), or in time to treatment failure (10 and 11 months). The overall estimated cure rate was 13%. An equal degree of myelosuppression was seen with the two regimens, whereas neuro- and nephrotoxicity were more pronounced when PH was given sequentially to CAF than with the alternating schedule. We conclude that the sequential and the alternated use of doxorubicin- and platinum-based regimens yield equivalent results and that other approaches should be investigated to improve treatment effects.

Adult

First-line chemotherapy with intraperitoneal cisplatin and intravenous cyclophosphamide in ovarian carcinoma. A preliminary report.

Between August 1982 and October 1986, the feasibility and activity of five cycles of intraperitoneal (i.p.) cisplatin (CDDP) (90 mg/m2 in 6 h dwelling) and i.v. cyclophosphamide (600 mg/m2) were studied in 24 previously untreated patients with ovarian carcinoma having small or no residual disease after cytoreductive surgery. Six patients (25%) had local complications requiring catheter removal before the end of therapy. Fifteen of the 21 patients (71%) evaluable for activity achieved or maintained a pathologic complete remission. The median disease-free survival was 29+ months (range 18-58+ months). Three patients with tumor progression (two patients previously without evidence of disease, and one patient with minimal residual disease), and three partial responders were documented by laparotomy at the end of therapy. Two patients who achieved pathologic complete response relapsed at 20 and 36 months. All treatment failures (eight cases, 38%) occurred in the peritoneal cavity. Since patients were selected for having the most favorable tumor characteristics to benefit from i.p. treatment, our findings may cast some doubt on the actual contribution of i.p. CDDP at a dose of 90 mg/m2 in the treatment of patients with ovarian carcinoma and small residual disease in the peritoneal cavity.

Adult

Downstaging of esophageal cancer after preoperative radiation and chemotherapy.

OBJECTIVE: This retrospective, nonrandomized review evaluates 125 patients with esophageal carcinoma (adenocarcinoma and squamous cell) who underwent either surgery only or preoperative chemotherapy and/or radiation therapy followed by surgery. Major end points were survival and postchemoradiation downstaging. METHODS: Forty-four patients underwent radiation therapy of 4500 cGy over 5 weeks. Fluorouracil and cisplatin were administered on the first and fifth week of radiotherapy. Ninety-eight patients underwent "potentially curative" resections-transhiatal esophagectomy (70), Lewis esophagogastrectomy (25), and left esophagogastrectomy (3). All patients with preoperative adjuvant therapy underwent endoscopy and biopsy before surgery. RESULTS: There were no differences in overall mortality (5%) or surgical complications in either group. Fourteen of 44 patients (32%) downstaged to complete pathologic response, with 5-year survival of 57%. Fifteen of 44 patients (34%) downstaged to microscopic residual tumor, with 1- and 3-year survival of 77% and 31%, respectively. Twenty-eight of 29 patients in the two downstaged groups were lymph node negative. Overall, 5-year survival in the adjuvant therapy plus surgery group versus surgery only was 36% and 11% (p = 0.04). Five-year survival in lymph node-negative adjuvant therapy and surgery patients was 49% (p = 0.005). Positive nodes in the surgery only group was 48% versus 23% in the adjuvant therapy and surgery group (p = 0.02). CONCLUSION: Although retrospective and nonrandomized, these results suggest that preoperative chemoradiation results in significant clinical and pathologic downstaging, increases survival, and may sterilize local and regional lymph nodes, accounting for both downstaging and survival statistics.

Adenocarcinoma

The next-generation biomarkers in early-stage triple negative breast cancer.

PURPOSE OF REVIEW: Despite maximal neoadjuvant chemoimmunotherapy, nearly 40% of early-stage triple-negative breast cancer (TNBC) patients fail to achieve pathological complete response, underscoring an urgent need for biomarkers capable of guiding treatment modulation. This review summarizes recent advances in tumor-infiltrating lymphocytes (TILs), circulating tumor DNA (ctDNA), and genomic signatures, exploring their potential integration into clinical decision-making. RECENT FINDINGS: TILs remain the most validated, cost-effective prognostic biomarker, although standardized scoring is still needed to overcome interobserver variability. ctDNA has emerged as a dynamic, real-time prognostic tool, with postneoadjuvant detection strongly predicting relapse and worse outcomes. Nonetheless, optimal sampling timing remains undefined. Genomic signatures, particularly TNBC-DX, provide standardized, reproducible prognostic information by integrating immune and proliferative gene expression. Emerging data suggest that combining these biomarkers may offer a complementary and synergistic effect. SUMMARY: Multibiomarker integration, supported by prospective validation and automated models, represents a promising approach to personalize treatment algorithms in early-stage TNBC, balancing efficacy and toxicity while guiding escalation and de-escalation strategies.

artificial intelligence

CA 125, placental alkaline phosphatase, and tissue polypeptide antigen in the monitoring of ovarian carcinoma. A comparative study of three different tumor markers.

Three different tumor markers, placental alkaline phosphatase (PLAP), tissue polypeptide antigen (TPA), and cancer antigen 125 (CA 125), were measured in serum samples obtained during chemotherapy in 57 ovarian carcinoma patients. At the start of chemotherapy, 37, 63, and 77% had elevated serum values of PLAP, TPA, and CA 125, respectively. During chemotherapy, changing PLAP serum levels reflected disease regression and, later, progression in only 2 patients. TPA serum levels reflected the disease course in 15 patients and CA 125 in 28 patients. Rising CA 125 values predicted disease progression in 12 patients for a median of 2 months. At second-look laparotomy, all 11 patients with pathological complete response were marker negative. In the remaining 46 patients with residual or progressive disease, 27, 50, and 61% had elevated serum levels of PLAP, TPA, and CA 125, respectively. None of the markers reflected microscopic disease or pure carcinomatosis. For management decisions, CA 125 was clearly the most useful of the markers. In this study no further information was gained from the other two markers.

Alkaline Phosphatase

Critical analysis of neoadjuvant therapy for Stage IIIa non-small cell lung cancer [corrected].

Lung cancer is the major cause of cancer mortality. Locally advanced (Stage III) disease constitutes 30 to 40% of the entire group of non-small cell lung cancer (NSCLC). Surgical resection offers the best opportunity for cure, but resection of disease is possible in only a minority of patients with Stage IIIa disease. Even among patients who have "successful" surgery systemic relapse is common, and the 5-yr survival after complete resection is only 30%. Preoperative (neoadjuvant) chemotherapy is under investigation in an attempt to improve the bleak outcome of patients with Stage IIIa NSCLC. Preliminary trials have shown that this approach is feasible: neoadjuvant treatment can be administered with moderate toxicity and in most cases without compromising the possibility for surgical resection. In some instances, neoadjuvant treatment has produced pathologic complete responses, and in others it has decreased tumor bulk so that inoperable patients became surgical candidates. Whether this latter phenomenon has an impact on survival is unknown. Therefore, the role of neoadjuvant treatment for locally advanced lung cancer will not be known until properly designed randomized trials are conducted.

Antineoplastic Combined Chemotherapy Protocols

A phase II study of combination chemotherapy in advanced ovarian carcinoma with cisplatin and cyclophosphamide plus reduced glutathione as potential protective agent against cisplatin toxicity.

AIMS AND BACKGROUND: The clinical use of cisplatin (CDDP), one of the most active agents in advanced ovarian cancer, is limited by nephrotoxicity and cumulative neurotoxicity. In preclinical studies, reduced glutathione (GSH) demonstrated a protective action against CDDP nephrotoxicity. We treated 20 patients with advanced ovarian carcinoma, with polychemotherapy containing CDDP + GSH, to assess the protective action of GSH against CDDP nephrotoxicity. METHODS: Between January 1988 and December 1989, 20 patients, with advanced ovarian carcinoma (St. III-IV-FIGO), not pretreated received CDDP: 45 mg/m2 i.v., on day 1-2, + cyclophosphamide (CPA): 900 mg/m2 i.v. on day 2 + GSH 2500 mg i.v. in normal saline 100 ml (in 15 min), before CDDP, every 21-28 days. RESULTS: A pathologic complete response rate (PCR) of 55% (11/20) was observed (7/14 patients with bulky disease). Median survival was 26.5 months and 5 patients were still alive and disease free at 35 months. Toxicity was limited, without any case of nephrotoxicity. CONCLUSIONS: On the basis of our previous experience with the same regimen without GSH, this study suggests that also in the clinical setting, GSH has no negative interference on CDDP activity and that GSH might improve the therapeutic index of CDDP. However, our data need to be confirmed by large randomized clinical studies.

Adult

Lactate dehydrogenase a is a crucial biomarker that affects the prognosis, chemotherapy effect, and immune infiltration of breast cancer.

PURPOSE: Lactate dehydrogenase A (LDHA) is a key node in tumor growth, metabolism, and invasion and is upregulated across multiple cancers. However, the molecular mechanisms by which LDHA influences breast cancer (BC) remain unclear. We analyzed public datasets and an institutional cohort to clarify the relationship between LDHA and BC, with the aim of informing future therapeutic strategies. PATIENTS AND METHODS: Using The Cancer Genome Atlas (TCGA), we assessed LDHA expression in BC and examined its associations with tumor mutational burden (TMB), immune cell infiltration, immune checkpoint molecules, and drug sensitivity. We integrated multiple databases and used Kaplan-Meier analyses to evaluate prognostic value. To explore biological functions of LDHA, we performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). We then analyzed BC patients receiving neoadjuvant chemotherapy (NAC) at Harbin Medical University Cancer Hospital to test the relationship between serum lactate dehydrogenase (LDH) and pathological complete response (pCR). Finally, we used National Health and Nutrition Examination Survey (NHANES) data to examine the association between serum LDH and mortality. RESULTS: LDHA was upregulated in BC tissues, and higher expression was significantly associated with worse overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). Functional analyses indicated enrichment of metabolic pathways, such as glycolysis. LDHA expression correlated with multiple immune cell populations, suggesting involvement in the tumor immune microenvironment. Lower LDHA expression was associated with greater sensitivity to several chemotherapeutic agents. In our institutional cohort, patients with lower serum LDH were more likely to achieve pCR, and LDH was an independent predictor of pCR. In NHANES, elevated serum LDH was linked to increased mortality risk. CONCLUSION: Our findings suggest that LDHA expression and serum LDH levels are promising prognostic biomarkers for survival and may predict chemotherapy response in BC patients. These results highlight the clinical relevance of LDHA-mediated metabolic pathways. However, as a correlational study, our findings warrant further validation through functional experiments to confirm LDHA's role as a potential therapeutic target.

Humans

Infants with neuroblastoma and regional lymph node metastases have a favorable outlook after limited postoperative chemotherapy: a Pediatric Oncology Group study.

PURPOSE: Infants less than or equal to 1 year of age with neuroblastoma (NB) have a favorable outlook with minimal to moderate therapy. Patients with complete or partial removal of the primary tumor but positive intracavitary lymph nodes (Pediatric Oncology Group [POG] stage C) have a higher risk for recurrent disease. To determine the importance of distinguishing infants with POG stage C NB from those with POG stage B disease and to assess the efficacy and toxicity of treating POG stage C infants with limited, postoperative chemotherapy, a study was conducted by the POG. PATIENTS AND METHODS: Forty-four eligible POG stage C infants received cyclophosphamide 150 mg/m2 orally on days 1 to 7 and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) 35 mg/m2 intravenously (IV) on day 8 (CYC/ADR), every 3 weeks for five courses followed by second-look surgery. No continuation therapy was given if surgical and pathologic complete response (CR) was achieved. Secondary therapy with five courses of cisplatin 90 mg/m2 on day 1 followed by teniposide (VM-26) 100 mg/m2 on day 3 (CDP/VM) was given to infants with gross residual tumor after CYC/ADR and second-look surgery. RESULTS: Thirty-four infants achieved CR after CYC/ADR alone, three after CYC/ADR and second-look surgery, two after CYC/ADR, surgery, and maintenance therapy, and two after alternative treatment with CDP/VM (total CR rate, 42 of 44). The 3-year survival and disease-free survival are both 93%. Toxicity was nominal. CONCLUSIONS: Infants with POG stage C NB have a favorable outlook, which is similar to infants with POG stage B NB; the surgical staging procedure for distinguishing these infant subsets may not be necessary. Future studies should focus on the reduction of treatment toxicity and efficacy maintenance, and address methods to identify infants at risk for failure.

Actuarial Analysis

High dose-rate intraluminal irradiation in bronchogenic carcinoma. Technique and results.

Patients who present with symptomatic airway obstruction often have limited therapeutic options. Intraluminal irradiation has been used in an attempt to obtain sustained palliation. Patients treated with high dose-rate endobronchial irradiation have shown good to excellent palliation of symptoms, as well as a high rate of local control; however, these results have not always been devoid of complications. Some recent reports have shown a high incidence of morbidity, including an excessive incidence of fatal pulmonary hemorrhage. In this series, we report on 80 high dose-rate endobronchial treatments in 32 patients who were treated with remote afterloading endobronchial irradiation. All patients had endoscopic and histologic proof of tumor. Patients were divided into two groups. Group 1 consisted of 17 patients who were treated with endobronchial brachytherapy as a boost to primary external-beam irradiation. The remaining 15 patients comprised group 2 and were treated for endobronchial recurrence after prior irradiation with an external beam (main dose, 5,000 cGy). The endobronchial irradiation treatments were delivered using a high dose-rate remote afterloader. The standard dose per fraction was 500 cGy prescribed at a distance of 1 cm from the central axis of the catheter for a median of 3 fractions at weekly intervals. Treatment length averaged 5 cm; the median total dose was 1,500 cGy. The median follow-up for the entire group was 9.3 months, with a range of 6 to 24 months. Symptomatic improvement was attained in 15 of 15 patients presenting with hemoptysis, in 6 of 7 of those with cough, and in 10 of 10 who presented with dyspnea. In ten patients, follow-up endoscopy was performed, which revealed a pathologic complete response (by negative results on biopsies). At 6 months past the last brachytherapy, clinical and radiographic local control was obtained in 15/17 (88 percent) of the patients in group 1 and in 70 percent of the patients in group 2. All patients tolerated treatment well, without any acute or late complications, and there were no instances of fistula formation or fatal pulmonary hemorrhage. There was no association between the location of recurrence and complications. Fractionation, dose per fraction, and total combined dose appear to be important parameters in reducing complications.

Brachytherapy