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Purpose: Pelvic lymph node metastases (ypN+) after multiagent neoadjuvant chemotherapy (NAC) is a poor prognostic sign in nonmetastatic muscle-invasive bladder cancer (nmMIBC). We sought to create a nomogram predicting probability of ypN+ after NAC for cN0 nmMIBC and determine association with overall survival (OS)., Methods and Materials: We reviewed the National Cancer Database for patients with cT2-4N0M0 urothelial carcinoma of the bladder receiving multiagent NAC and surgery from 2004 to 2020. Following a data split, univariate logistic regression identified variables associated with ypN+ at P < .05. Eligible variables were used for multivariate logistic regression and nomogram generation. A threshold for 95% sensitivity defined high- and low-risk groups for ypN+. Fine-Gray models assessed ypN+ risk group and OS, accounting for competing risks of surgical mortality., Results: A total of 6194 patients were identified with a median follow-up of 39.5 months (interquartile range [IQR], 20.5-67.2 months). Most patients had high-grade (97.7%) cT2 disease (70.8%) with nonpapillary urothelial histology (67.3%) and initiated NAC at a median of 41.0 days after diagnosis (IQR, 28.0-59.0 days).The nomogram included age in decades (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.87-1.03; P = .172), weeks from diagnosis to NAC (OR, 1.02; 95% CI, 1.01-1.04; P = .004), nonpapillary histology (OR, 1.17; 95% CI, 0.99-1.39; P = .068), and clinical T-stage. Within the testing cohort, ypN+ was found in 392 (22.8%) high-risk and 12 (8.0%) low-risk patients ( P < .001), with median OS of 36.1 and 74.0 months, respectively ( P < .001). High-risk patients had worse OS despite competing risks of 30-day (subdistribution hazard ratio [SHR], 1.80; 95% CI, 1.49-2.18; P < .001) and 90-day surgical mortality (SHR, 1.68; 95% CI, 1.39-2.04; P < .001)., Conclusions: This is the first study to provide a tool for predicting ypN+ and prognosticate worse OS in primarily high-grade nmMIBC and could select patients for alternative neoadjuvant therapy and facilitate future study., Competing Interests: Arash Rezazadeh reports a relationship with ECOM Medical that includes: equity or stocks. Arash Rezazadeh reports a relationship with Exelixis Inc that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Arash Rezazadeh reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Arash Rezazadeh reports a relationship with Bayer Corporation that includes: consulting or advisory, funding grants, and travel reimbursement. Arash Rezazadeh reports a relationship with Pfizer that includes: consulting or advisory, funding grants, and travel reimbursement. Arash Rezazadeh reports a relationship with Novartis that includes: consulting or advisory, speaking and lecture fees, and travel reimbursement. Arash Rezazadeh reports a relationship with Genentech that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Arash Rezazadeh reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory, funding grants, and speaking and lecture fees. Arash Rezazadeh reports a relationship with EMD Serono Inc that includes: consulting or advisory and speaking and lecture fees. Arash Rezazadeh reports a relationship with Immunomedics that includes: consulting or advisory and funding grants. Arash Rezazadeh reports a relationship with Gilead Sciences Inc that includes: consulting or advisory and speaking and lecture fees. Arash Rezazadeh reports a relationship with Janssen Pharmaceuticals Inc that includes: funding grants, speaking and lecture fees, and travel reimbursement. Arash Rezazadeh reports a relationship with Astellas Medivation that includes: funding grants, speaking and lecture fees, and travel reimbursement. Arash Rezazadeh reports a relationship with Sanofi-Aventis US LLC that includes: speaking and lecture fees. Arash Rezazadeh reports a relationship with Eisai Inc that includes: funding grants, speaking and lecture fees, and travel reimbursement. Arash Rezazadeh reports a relationship with Amgen Inc that includes: speaking and lecture fees. Arash Rezazadeh reports a relationship with Exelixis Inc that includes: funding grants, speaking and lecture fees, and travel reimbursement. Arash Rezazadeh reports a relationship with Merck & Co Inc that includes: speaking and lecture fees. Arash Rezazadeh reports a relationship with Astellas Pharma US Inc that includes: funding grants, speaking and lecture fees, and travel reimbursement. Arash Rezazadeh reports a relationship with AVEO Oncology that includes: speaking and lecture fees. Arash Rezazadeh reports a relationship with MacroGenics Inc that includes: funding grants. Arash Rezazadeh reports a relationship with Myovant Sciences Inc that includes: speaking and lecture fees. Arash Rezazadeh reports a relationship with BeyondSpring Inc that includes: funding grants. Arash Rezazadeh reports a relationship with BioClin Therapeutics that includes: funding grants. Arash Rezazadeh reports a relationship with Clovis Oncology that includes: funding grants. Arash Rezazadeh reports a relationship with Bavarian Nordic Inc that includes: funding grants. Arash Rezazadeh reports a relationship with Seagen Inc that includes: funding grants and speaking and lecture fees. Arash Rezazadeh reports a relationship with Epizyme Inc that includes: funding grants. Nataliya Mar reports a relationship with Seagen Inc that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma ( n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients.

Twenty-three targets in 16 patients treated with stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) were analyzed in terms of dosimetric homogeneity, target conformity, organ-at-risk (OAR) sparing, monitor unit (MU) usage, and beam-on time per fraction using RapidArc volumetric-modulated arc therapy (VMAT) vs. multifield sliding-window intensity-modulated radiation therapy (IMRT). Patients underwent computed tomography simulation with site-specific immobilization. Magnetic resonance imaging fusion and optical tracking were incorporated as clinically indicated. Treatment planning was performed using Eclipse v8.6 to generate sliding-window IMRT and 1-arc and 2-arc RapidArc plans. Dosimetric parameters used for target analysis were RTOG conformity index (CI(RTOG)), homogeneity index (HI(RTOG)), inverse Paddick Conformity Index (PCI), D(mean) and D5-D95. OAR sparing was analyzed in terms of D(max) and D(mean). Treatment delivery was evaluated based on measured beam-on times delivered on a Varian Trilogy linear accelerator and recorded MU values. Dosimetric conformity, homogeneity, and OAR sparing were comparable between IMRT, 1-arc RapidArc and 2-arc RapidArc plans. Mean beam-on times ± SD for IMRT and 1-arc and 2-arc treatments were 10.5 ± 7.3, 2.6 ± 1.6, and 3.0 ± 1.1 minutes, respectively. Mean MUs were 3041, 1774, and 1676 for IMRT, 1-, and 2-arc plans, respectively. Although dosimetric conformity, homogeneity, and OAR sparing were similar between these techniques, SRS and SBRT fractions treated with RapidArc were delivered with substantially less beam-on time and fewer MUs than IMRT. The rapid delivery of SRS and SBRT with RapidArc improved workflow on the linac with these otherwise time-consuming treatments and limited the potential for intrafraction organ and patient motion, which can cause significant dosimetric errors. These clinically important advantages make image-guided RapidArc useful in the delivery of SRS and SBRT to intracranial and extracranial targets., (Published by Elsevier Inc.)

Primary leptomeningeal oligodendrogliomas (PLOs) are rare intracranial malignancies where tumors grow in the subarachnoid space without an obvious connection to the brain or spinal cord parenchyma. Adding to the three previously reported cases of PLO with no parenchymal involvement we report a fourth case of the same in this paper in a 50-year-old woman presenting with unrelenting headaches. CT scan of her head revealed hydrocephalus and MRI revealed diffuse enhancement of her leptomeninges throughout her brain and spine, prominent over the basilar region. Biopsy obtained using a frameless stereotactic biopsy showed sharply defined cell borders, clear cytoplasm, and rounded nuclei consistent with an oligodendroglioma. Our case suggests that PLO can mimic diffuse forms of granulomatous meningitis and should be suspected in patients that clinically and radiographically present like granulomatous meningitis but without blood or CSF markers for the same.

Objectives: Topotecan improves response rate (RR), progression-free survival (PFS) and overall survival (OS) when added to cisplatin in treating metastatic and recurrent cervical cancer. The objective of this study was to assess the feasibility of adding weekly topotecan to cisplatin in patients with primary, locally advanced carcinoma of the cervix receiving pelvic irradiation., Methods: Patients with primary, previously untreated, histologically confirmed invasive squamous cell, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, stages IB2-IVA were treated with external beam pelvic radiotherapy (45 Gy), intracavitary low dose rate brachytherapy (40 Gy) and a parametrial boost (5.4-9 Gy) with overall treatment time not to exceed 8 weeks. Concurrent chemotherapy was IV cisplatin 40 mg/m(2)plus IV topotecan 2 mg/m(2) on days 1, 8, 15, 22, 29 and once during parametrial boost for 6 cycles. Patients were monitored with history, physical examination, tumor measurement and laboratory evaluation before entering the study, before each cycle of chemotherapy, at study termination and every three months thereafter., Results: The study met its accrual goal of 12 patients. With a median follow-up of 22 months, eleven patients completed treatment and ten are in long term follow up without evidence of recurrent disease. The 12th patient developed progressive disease during therapy. All patients completed at least 4 cycles of chemotherapy, with the majority (82%) completing 5 or more. Grade 2 or higher neutropenia delayed treatment in 54% of cycles. The median treatment delay was 1.5 cycles (range: 1 to 5 cycles). Median treatment time was 59 days (range 46 to 81 days). The complete RR was 92% (95% confidence interval, 55%-100%)., Conclusions: The addition of weekly topotecan to cisplatin at this dose and schedule during pelvic irradiation for locally advanced cervical cancer appears to be feasible. Based on this primary treatment data and the activity of cisplatin-topotecan in the recurrent disease setting, phase II and III studies of this combination are warranted.

This is a retrospective analysis of a new treatment modality, intra-arterial administration of Yttrium-90 TheraSphere, for unresectable hepatocellular carcinoma (HCC). Patients with HCC not amenable to surgical treatment who had satisfactory physiological function without comorbid disease or significant pulmonary shunting were eligible for treatment. Patients were categorized into complete, partial, or no response based on serum alpha-fetoprotein (AFP) levels and CT or MRI imaging. Fourteen patients were considered candidates for treatment. Three patients were excluded due to significant hepatopulmonary shunting. Eleven patients were treated with TheraSphere. One patient (9%) had a complete response, eight patients (78%) had a partial response, and two patients (18%) showed no response. Partial and complete responders with AFP-associated HCC demonstrated a median decrease in AFP levels of 79 per cent at 73 days. No patients developed liver toxicity nor died due to treatment. Five patients (45%) died of progressive disease at a median of 7 months post-treatment. Six patients (54%) were alive at a median of 11 months (range, 9 to 20 months). Okuda stage 2 and 3 patients showed a median survival of 11 months and 7 months, respectively. Yttrium-90 TheraSphere treatment for unresectable hepatocellular carcinoma is well tolerated and appears to extend survival.

The purpose of this work is to evaluate our initial experience in treating previously irradiated, recurrent head-and-neck cancers using intensity-modulated radiotherapy (IMRT). Between July 1997 and September 1999, 12 patients with previously irradiated, locally recurrent head-and-neck cancers were treated with IMRT. These included cancers of the nasopharynx, oropharynx, hypopharynx, larynx, paranasal sinus, skin of the head-and-neck region, and malignant melanoma. Five of these 12 patients had received radiation as the primary treatment, with doses ranging from 66.0 to 126.0 Gy, and the remaining 7 patients had undergone definitive surgeries followed by an adjuvant course of radiation treatment, with doses ranging between 36.0 and 64.8 Gy. Recurrence after the initial course of radiation occurred in periods ranging from 4 to 35 months, with 11 of 12 cases recurring fully in the fields of previous irradiation. Recurrent tumors were treated with IMRT to total doses between 30 to 70 Gy (> 50 Gy in 10 cases) prescribed at the 75% to 92% isodose lines with daily fractions of 1.8 to 2 Gy. The results revealed that acute toxicities were acceptable except in 1 patient who died of aspiration pneumonia during the course of retreatment. There were 4 complete responders, 2 partial responders, and 2 patients with stable disease in the IMRT-treated volumes. Three patients received IMRT as adjuvant treatment following salvage surgery. At 4 to 16 months of follow-up, 7 patients were still alive, with 5 revealing no evidence of disease. In conclusion, this pilot study demonstrates that IMRT offers a viable mode of re-irradiation for recurrent head-and-neck cancers in previously irradiated sites. Longer follow-up time and a larger number of patients are needed to better define the therapeutic advantage of IMRT in recurrent, previously irradiated head-and-neck cancers.

Radiation treatment of malignant diseases of the spine poses unique challenges to the radiation oncology treatment team. Intensity-modulated radiation therapy (IMRT) offers the capability of delivering high doses to targets near the spine while respecting spinal cord tolerance. At the University of California, Irvine, 8 patients received a total of 10 courses to the spine for a variety of primary and metastatic malignant conditions. This paper discusses anatomical considerations, spinal cord radiation myelopathy, and treatment planning issues as it relates to the treatment of spinal cord lesions. Between October 1997 and August 2001, a total of 8 patients received 10 courses of IMRT for primary or metastatic disease of the spine. Cancers treated included metastatic lung, renal, adrenocortical cancers, and primary sarcomas and giant cell tumor. Five cases had 6 courses given for re-irradiation of symptomatic disease and 3 cases had 4 courses of IMRT as primary management of their spinal lesions. Although 3 courses were given postoperatively, these were for grossly residual disease. For the re-irradiation patients, the mean follow-up interval was 4 months. The local control was estimated at 14%. Of the patients treated with primary intent, the mean follow-up was 9 months and the local control rate 75%. No patients developed spinal cord complications.

Background: The Mayer-Rokitansky-Kuster-Hauser syndrome occurs in 1 in 4000 to 5000 female births. Primary vaginal cancer constitutes less than 2% of all malignancies of the female genital tract. A report of the first case of the unlikely occurrence of both of these developments in the same patient is presented., Case: A 34-year-old nulligravid Philippine woman with a history of Mayer-Rokitansky-Kuster-Hauser syndrome presented with a 5-month history of bleeding from a blind vaginal pouch. Vaginal biopsy identified a moderately differentiated endometrioid adenocarcinoma. Exploratory laparotomy, bilateral salpingo-oophorectomy, pelvic and iliac lymph node samplings, and excision of a mullerian remnant were performed with no evidence of disease. A FIGO Stage I vaginal cancer was assigned and pelvic irradiation was given. Disease recurred 4 months later and the patient underwent total pelvic exenteration. More than 1 year since the exenteration procedure, she is without evidence of disease., Conclusion: This is the first reported case of a primary vaginal cancer in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome. It is a reminder that routine gynecologic examinations are still warranted as these patients are at risk for malignant changes in residual mullerian tissues., ((c) 2002 Elsevier Science (USA).)

Background: Because primary carcinoma of the vagina comprises less than 2% of all gynecologic malignancies, the reported experience in the treatment of large numbers of patients is available only from a few major centers and most often encompasses a variety of differences in treatment selection and technique. The objective of this study was to assess the long term results of an interstitial iridium-192 afterloading implant technique using the Syed-Neblett dedicated vaginal plastic template., Methods: Patients who were treated from 1976 to 1997 were examined retrospectively., Results: Seventy-one patients underwent interstitial implantation with (n = 61 patients) or without external beam radiotherapy. The median age was 59 years (range, 16-86 years). Patients were staged according to the International Federation of Gynecology and Obstetrics system and included Stage I (n = 10 patients), Perez modification Stage IIA (n = 14 patients), Perez modification Stage IIB (n = 25 patients), Stage III (n = 15 patients), and Stage IV (n = 7 patients). Each implant delivered an approximately 20-gray (Gy) minimum tumor dose, with the total tumor dose reaching 80 Gy with integrated external beam radiotherapy. Local control was achieved in 53 patients (75%). The median follow-up was 66 months (range, 15-163 months), and the 2-year, 5-year, and 10-year actuarial disease free survival rates are 73%, 58%, and 58%, respectively. By stage, 5-year disease free survival rates included Stage I, 100% of patients; Stage IIA, 60% of patients; Stage IIB, 61% of patients; Stage III, 30% of patients; and Stage IV, 0% of patients. The factors disease stage and primary lesion size independently influenced the survival rates. Significant complications occurred in 9 patients (13%) and included necrosis (n = 4 patients), fistulae (n = 4 patients), and small bowel obstruction (n = 1 patient)., Conclusions: Interstitial irradiation can effect local control in the majority of patients with primary carcinoma of the vagina with acceptable morbidity. Long term cure is demonstrable in patients with Stage I-III disease., (Copyright 2001 American Cancer Society.)