bluuebunny/crossref_metadata_2025 huggingface dataset:
Interstitial high dose rate (HDR) brachytherapy under local anesthesia for early stage prostate cancer
Authors: White D. , Mark R. , Anderson P. J. , Neumann T. , Nair M.
Published: March 2020

14639

Background: Transrectal Ultrasound (TRUS) guided interstitial implant for prostate cancer using Low Dose Rate (LDR) and High Dose Rate (HDR) techniques has been reported with results comparing very favorably to external beam radiation therapy. TRUS interstitial implant of the prostate has been traditionally performed under general or spinal anesthetic in an operating room. We report our results with a technique performed under local anesthesia in a Department procedure room. Methods: Patients with T1 and T2 localized prostate cancer were judged to be candidates for TRUS guided interstitial implant. Results: Between 2002 and 2006, 248 TRUS guided prostate implants were performed under local anesthesia. Conscious sedation consisted of intravenous Morphine (12–22 mg) and Versed (6–14 mg), or intravenous Demerol (50–175 mg) and Versed (3–12 mg). Local anesthetic was given with a mixture of 1% Lidocaine, 0.25% Marcaine, 1:100,000 Epinephrine, and 4% Sodium Bicarbonate neutralizing solution (20–120 cc). Local anesthesia was given to a 5 × 5 cm perineal area to a depth of 10 cm under TRUS guidance. The implants were placed under mobile multi-plane prostate template (Radiation Therapy Products Prostate Template) guidance using from 3 to 4 planes, and 12 to 22 needles. Needle spacing was 1.0 cm. The implant procedure included sigmoidoscopy and cystoscopy. Median implant time was 45 minutes (range: 30 to 150 minutes). HDR treatment was given using the Nucletron afterloading system. The implant volume received 2,250 cGy in 3 fractions prescribed to the 100% Isodose line, given over 24 hours. Urethral dose points (12–16) were followed, and limited to ≤ 105% of the prescription dose. The procedure was well tolerated, with all patients having completed the procedure. One patient developed respiratory suppression, and required reversal with Narcan. He recovered uneventfully. Otherwise, there have been no acute complications to date. Conclusions: TRUS interstitial implant of the prostate under local anesthesia is feasible. Implant time and complications compare favorably to general or spinal anesthetic technique.

No significant financial relationships to disclose.
Effectiveness of zoledronic acid for the prevention of bone metastases in high risk prostate cancer patients: A randomised, open label, multicenter study of the European Association of Urology (EAU) in cooperation with the Scandinavian Prostate Cancer Group (SPCG) and the Arbeitsgemeinschaft Urologische Onkologie (AUO). An initial report of the “ZEUS” study
Authors: Witjes W. , Tammela T. , Wirth M.
Published: March 2020

14644

Background: Patients with advanced prostate cancer (PC) are at high risk of developing bone metastases resulting in clinically significant skeletal morbidity and debilitating bone pain. Zoledronic acid (ZA) significantly reduced the incidence and delayed the onset of skeletal complications and provided durable pain reduction compared with placebo in patients with PC metastatic to bone. Methods: We started a European study investigating the effect of ZA in the prevention of PC bone metastases in patients with high risk PC. This prospective, multi-centre, randomised, open-label study, the ZA EUropean Study (ZEUS), aims at randomising 1300 patients within 3 years in 13 European countries and Turkey. Patients are randomised for standard PC therapy plus 4 mg ZA intravenously every 3 months for a period of 48 months or standard PC therapy alone. Results: Presently, we have randomised 484 patients with a mean age of 67 years (range 45–86) in 13 countries. All patients had at least one of the following high risk prognostic factors: 281 (58%) patients had a PSA ≥ 20 ng/ml, 140 (29%) patients had lymphnode positive disease and 286 (59%) patients had a Gleason of 8–10. 124 (26%) patients had a PSA ≥ 20 ng/ml and a Gleason of 8–10; 60 (12%) patients had a PSA ≥ 20 ng/ml and N1 disease and 64 (13%) patients had a Gleason of 8–10 and N1 disease. 244 (50%) patients underwent a prior prostatectomy or radiotherapy with curative intent and 303 (63%) patients received hormonal treatment. The randomisation arms were equally distributed amongst prognostic groups, centres and countries. Conclusions: The ZEUS study is designed to evaluate if ZA can contribute in preventing or delaying bone metastases in high risk PC patients. Presently, the majority (59%) of patients have a Gleason of 8–10 or a PSA ≥ 20 ng/ml (58%) and they receive hormonal treatment (63%). Half (50%) of the patients underwent a prior prostatectomy or radiotherapy with curative intent. This is representative for the PC population that is at high risk for developing bone metastases.

No significant financial relationships to disclose.
Clinical outcome of postchemotherapy salvage surgery for metastatic germ cell tumors in Japan
Authors: Kakimoto K. , Kinouchi T. , Ono Y. , Meguro N. , Maeda O. , Usami M. , Nonomura N. , Oka D. , Miki T. , Mizutani Y.
Published: March 2020

14654

Background: Salvage surgery including retroperitoneal lymph node dissection (RPLND) following chemotherapy has been considered a critical component in the comprehensive management of advanced germ cell tumors (GCT). The objectives of this study were to determine the pathologic findings and clinical outcome of patients with metastatic GCT who underwent postchemotherapy salvage surgery. Methods: From 1980 to 2004, 157 patients with metastatic diseases underwent postchemotherapy salvage surgery at three institutions. Surgical resection was indicated in the presence of residual radiographic abnormalities. The cause-specific survival rate was calculated using the Kaplan-Meier method. Results: The histology of GCT was pure seminoma in 49 patients and non-seminoma in 108 patients. As first-line chemotherapy, 30 patients were treated with PVB (cisplatin, vinblastine and bleomycin) regimen, 107 patients with PEB (cisplatin, etoposide and bleomycin) regimen and 20 patients with other regimens. Salvage surgery was performed after first-line chemotherapy in 87 patients and after salvage chemotherapy in 70 patients. As salvage surgery, RPLND was performed in 135 patients, resection of pulmonary metastasis in 38, hepatotomy in 2 and resection of metastatic brain tumors in 3. The pathological findings at surgery were necrosis in 87 (55%) patients, mature teratoma in 34 (22%) and residual cancer in 36 (23%). Five of 36 patients with residual cancer performed salvage surgery in the state of marker positive. Of the 31 patients who had residual cancer with normalized marker, salvage surgery was performed after salvage chemotherapy in 11 patients. The sites of residual cancer were retroperitoneal lymph nodes in 34 patients, lung in 4, brain in 2 and liver in 1. The cause-specific 5-year survival rates for patients who had necrosis, mature teratoma and residual cancer were 95%, 96% and 68%, respectively. Conclusions: Residual cancer could not reliably be predicted or discriminated from necrosis or mature teratoma. Therefore, salvage surgery to remove postchemotherapy residual masses remains essential in the successful treatment of metastatic GCT.

No significant financial relationships to disclose.
Phase I-II trial of irinotecan (CPT) and cisplatin (P) as concurrent chemo-radiotherapy (CCRT) for patients (pts) with primary local advanced cervical cancer (LACC): A KCOG 0328 trial
Authors: Ito K. , Kita M. , Hosokawa K. , Toyoda S. , Kozuki M. , Hayashi M. , Takata T. , Miyoshi Y. , Koshiba H. , Tabata T.
Published: March 2020

15002

Background: Though CCRT based on P is now recommended in LACC, there is no standard regimen. We conducted a phase I-II trial of CPT and P as CCRT in pts with primary LACC. Methods: Eligibility criteria: histologically confirmed primary LACC as FIGO stage III to IVb by para-aortic lymphnode (PAN) metastasis, age 16–75 years, ECOG performance status <2, adequate bone marrow, hepatic and renal function, and written informed consent. Radiotherapy (RT) consisted of external beam 5040cGy in 28 fractions followed by single application brachytherapy, delivering 1800–2400 cGy to point A in 3–4 fractions. The doses of chemotherapy (CT) were set up as follows: dose level (DL) 0; CPT 20 mg/m2, P 30 mg/m2, DL1; CPT 25mg/m2, P 30 mg/m2, DL2; CPT 30 mg/m2, P 30 mg/m2, and the starting level was chosen DL1. CT was curried out weekly 5 cycles concurrently with RT. Toxicities were assessed according to NCI-CTC ver2.0J and responses were assessed according to RECIST. Results: So far 9 pts have been entered. The median age was 52 years (range 29 -73). All pts were FIGO stage IIIb and histrogically squamous cell carcinoma. Among the first 2 pts in DL1, 2 dose-limiting toxicities (DLT) were observed (delay of treatment due to grade 3 diarrhea and nausea) resulting in dose reduction to DL0. In the next 3 pts in DL0, no DLTs were observed and the study is ongoing as phase II. All pts were evaluable for response and toxicity. Eight complete (CR) and 1 partial response (PR) were seen at target region of cervix. But 2 pts showed progressive disease (PD) at non-target region of PAN, lung and liver, then overall response rate assessed by RECIST was 77.8% (CR 7, PD 2). Now the median follow up period is 16 months (range 6 -30). So far 2 pts of PD died and 3 pts relapsed. The median survival time is 10+ months (range 6+ -30+). Toxicity in DL0 was observed febrile neutropenia in 1 pt only. Conclusions: The CCRT with CPT and P in DL0 is feasible and shows promising activity in pts with primary LACC.

No significant financial relationships to disclose.
Feasibility study of neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for stage III/IV ovarian, tubal and peritoneal cancers: Japan Clinical Oncology Group study JCOG0206
Authors: Onda T. , Kamura T. , Hirakawa T. , Kuzuya K. , Hatae M. , Iwasaka T. , Konishi I. , Katsumata N. , Fukuda H. , Yoshikawa H.
Published: March 2020

15020

Background: Retrospective analyses revealed that survival of ovarian cancer patients treated with NAC followed by IDS was comparable with those treated by standard treatment starting with primary debulking surgery. The purpose is to assess the safety and efficacy of the NAC setting treatment and also to know whether we can accurately diagnose the cancer by imaging studies, cytologic findings and tumor markers without diagnostic laparoscopy (DLS). Methods: The study was performed as a multi-institutional non-randomized phase II trial. Eligibility included stage III/IV müllerian carcinoma (MC) such as ovarian, tubal and peritoneal carcinomas diagnosed by imaging studies (CT and/or MRI), cytology of ascites, pleural effusions or fluids obtained by tumor centesis, CA125 >200 U/ml and CEA<20 ng/ml. After study enrollment, DLS is performed to confirm tumor origin, histology and stage. Four cycles of combination of paclitaxel (175 mg/m2, 3h) and carboplatin (AUC 6) are administered as NAC, followed by IDS and additional 4 cycles of chemotherapy. Primary endpoint is proportion of clinical complete remission (% cCR) with CA 125<20 U/ml among all stage III/IV MC confirmed by DLS (expected % cCR of 40% and threshold % cCR of 20%). Major secondary endpoint is positive predictive value (PPV) of clinical diagnoses concerning origin, histology and stage (expected PPV>90%, then DLS will be omitted in the next phase III study). The planned sample size was 56 eligibles, which gives 10% or lower Bayesian posterior probability that PPV is < 90% in case of three false positives. Results: Fifty six patients were enrolled between Jan/2003 and Feb/2004. All patients had accurate pre-DLS diagnosis concerning origin and histology. In 53 (PPV 94.6%) of 56 patients, tumor stage was accurately diagnosed. Twenty nine (62%) of 47 patients who underwent IDS had complete resection without residual tumors. Nineteen (%cCR 36%) among 53 patients with stage III/IV MC achieved cCR at completion of planned treatment. Conclusions: NAC starting without DLS followed by IDS for advanced MC is a promising treatment to be compared with the current standard treatment in a phase III study.

[Table: see text]
Survival and prognostic factors in patients with epithelial ovarian cancer receiving paclitaxel and carboplatin as first-line chemotherapy in Japanese women: A multi-center retrospective study
Authors: Kajiyama H. , Kikkawa F. , Kawai M. , Mizuno K. , Kobayashi I. , Kinoshita Y. , Matsuzawa K. , Kamiya N. , Inoue T. , Sakakibara T.
Published: March 2020

15022

Background: The aim of this retrospective study was to re-evaluate, multi-analytically, survival and prognostic factors of patients with epithelial ovarian cancer (EOC) receiving the combination of paclitaxel and carboplatin (PC). Methods: Between 1/00 and 12/04, a total of 335 cases with EOC of FIGO stage I-IV are registered in a multi-institutional series. All patients received cytoreductive surgery and combination chemotherapy of paclitaxel 180 mg/m2/3 hr and carboplatiion AUC = 5 for a total of 6 cycles. We retrospectively analyzed progression-free survival (PFS) and overall survival (OS) of these patients by stratification of assumable several prognostic factors and second-line regimen. Survival probabilities were estimated by Kaplan-Meier methods, and prognostic factors for survival were evaluated by a COX proportional hazard model. Results: Median age was 54 ± 11 years (range 9–81). The 3-, 4- and 5-year OS in patients was 67.0%, 53.9% and 50.6%, respectively. In a COX analysis, FIGO stage, histological type and residual tumor (2 cm < vs. 2 cm >; P = 0.0007, HR; 2.4, 95% CI = 1.4–4.0) were found to be independent significant factors for OS. The stratification analysis revealed that stage III-IV patients with clear cell and mucinous carcinoma have poorer prognosis than those with other histological types ( Table ). In contrast, no differences in histological grade (G1 vs. G2; P = 0.82, HR; 0.9, 95% CI = 0.5–1.6, G1 vs. G3; P = 0.65, HR; 0.9, 95% CI = 0.4–1.6) and kinds of second-line regimen were noticed for PFS and OS. Conclusions: Optimal surgical debulking, clinical stage, and histology appear to be important prognostic factors of survival in patients with EOC. This retrospective study suggests that PC may still have an impact on outcome. However, further strategy will be needed for improving survival of mucinous and clear-cell type EOC, especially with advanced stage.

[Table: see text]

No significant financial relationships to disclose.
Results of invasive cervical cancer patients undergoing inadvertent hysterectomy followed by salvage radiotherapy
Authors: Goel A. , Goel V. , Singh J. K.
Published: March 2020

15034

Background: Ca cervix is the leading gynecologic malignancy in India. Conventional treatment consists of radical hysterectomy or primary radiotherapy. Due to inadequate preop workup, invasive ca cervix has been incidentally found in surgical specimens after simple hysterectomy. Extrafascial hysterectomy is not curative as paracervical, paravaginal soft tissues & vaginal cuff are not removed. It is technically difficult to perform adequate radical surgery after a previous simple hysterectomy. It is critical that these patients receive postop RT immediately after surgery; otherwise the prognosis is much worse. Methods: Retrospective analyses of 68 patients of ca cervix referred to our Institute after simple hysterectomy for presumed benign or preinvasive cervical disease was done. The median age was 44 yrs (35–65). 18 pts (26.5%) were pre menopausal while 50 (73.5%) were post menopausal. Exact postop staging was not possible; however 40 pts (59%) had residual growth at vault, 4 had involvement of vagina and in 18 cases parametrial infiltration was evident. Postop USG showed median tumor size of 4.4 cm, hydronephrosis in 17.6% & bladder infiltration in 5.8% pts. Histopathology was squamous cell carcinoma in 97% cases. Results: All patients were treated with EBRT to whole pelvis (dose 50 Gy/25 Fr to 50.4 Gy/28 Fr) over 5-weeks, followed by central vaginal surface HDR brachytherapy (Dose 21 Gy/3 Fr). At an average follow up of 18 to 24 months post RT residual disease was present in 2 (2.9%), local recurrence in 6 (8.6%), scar recurrence in 2 (2.9%) and distant failures in 4 patients (5.8%). Radiation proctitis developed in 2, SAIO in 2, RVF in one and VVF in one patient. All local and distant failures were seen in patients with residual disease before starting RT. Poor response to RT was seen in patients elder than 40 years and when OTT was more than 75 days. No significant correlation was seen between local response rate and type or grade of tumor. Conclusion: Survival for patients with no residual cancer after simple hysterectomy is favorable; & poor for those with gross disease at the start of post hysterectomy treatment. EBRT combined with one or two fractions of intravaginal brachytherapy in the immediate postop period can achieve satisfactory disease control.

No significant financial relationships to disclose.
Efficacy of a gemcitabine based multiagent chemotherapy regimen for advanced uterine sarcomas
Authors: Singhal P. K. , Sharma S. , Benitez M. , Odunsi K. , Lele S.
Published: March 2020

15047

Background: Advanced stage uterine sarcomas (US) have poor prognosis. Active agents in US are doxorubicin, cisplatin and ifosfamide, with response rates (RR) of 25%, 19%, and 17% respectively. Given the poor response, there remains a need for other drugs. Gemcitabine has shown activity in soft tissue sarcomas. In trials with all subtypes of sarcomas, RR observed with single and multiagent schedules are ranging from 3 to 53%. There is scarce data on the use of gemcitabine in US. Aim of our study was to determine the clinical activity of gemcitabine based regimen in patients with US. Methods: From 2002–2005, data from11 chemotherapy naïve patients diagnosed with advanced stage US was reviewed who were receiving gemcitabine/ifosfomide/platinum (GIP) combination chemotherapy regimen in an adjuvant setting after TAH and surgical staging. Ifosfomide 2gm/m2 and Platinum 20 mg/m2 intravenously on days 1, 2 and 3. Gemcitabine 800 mg/m2 intravenously was administered on day 1 of a 28-day cycle. Results: Eleven pts were treated, all stages III and IV. The median age was 49 years. There were 6 carcinosarcomas, 4 LMS, and 1 ESS. Performance status was 0 (6 pts), 1 (5 pts). Four pts (36%) had undergone prior radiotherapy. The site of measurable disease in 10 pts (91%) was in the pelvis. The median number of GIP cycles received per pt was 6 (range 1–9). There were no treatment-related deaths. Hematologic toxicities of > Grade 3 were seen in 82% of pts and consisted of leukopenia and anemia. 36% of pts had an episode of febrile neutropenia. Neurotoxicty (Grade 3 in 2 pts), nausea (Grade 1/2 in 6 pts), and fatigue (Grade 1/2 in 7 pts) were observed. Three (27%) complete responses were observed, four pts had a partial response (36%), for an overall RR of 63%. Four pts had progression of disease (36%). Of the 7 pts demonstrating a response, 4 had previously been irradiated and 3 had not, such that the RR in those previously irradiated was 4/4 = 100% versus 3/7 = 43% in those not previously irradiated. Conclusions: The combination of GIP is well-tolerated and seems to be active in US, yielding RR higher than seen with single agent chemotherapy agents. Pts that received previous adjuvant radiation demonstrated the best responses to this regimen. A randomized trial is needed to evaluate the true value of this regimen in advanced stage US.

No significant financial relationships to disclose.
Glassy cell carcinoma of the uterine cervix
Authors: Restivo A. , Disilvestro P. , Moore R. , Weitzen S. , Kaufman S. , Puthawala Y. , Granai C. , Gordinier M.
Published: March 2020

15050

Background: Glassy Cell Carcinoma of the uterine cervix is a rare, aggressive form of cervical cancer accounting for only 1–5% of all cervical carcinomas. To date, there is no consensus on treatment modalities, but most advocate for a more aggressive treatment strategy including both radical surgery and radiation therapy. The objective of this study was to analyze the clinical features, treatment, and outcome of patients with Glassy cell carcinoma diagnosed at our institution. We hypothesized that such aggressive therapies yield survival benefits which approximate those of the more common squamous cell carcinomas of the cervix. Methods: In collaboration with the Department of Radiation Oncology at Rhode Island Hospital, a retrospective comprehensive chart review of all patients diagnosed with Glassy cell carcinoma of the cervix between the years 1993 and 2005 was undertaken at Women and Infant’s Hospital, Providence, RI. All cases were assessed for clinicopathologic features, treatment strategies, and outcome, including progression free survival and overall survival rates. Results: Twenty-eight patients with biopsy proven Glassy Cell Carcinoma of the cervix were identified. Eleven (39%) were less than age 40, and five (18%) were less than age 30. Of these, 19 were either stage IB or IIA, and 15/19 (79%) received multimodality therapy, a combination of radiation, chemotherapy, and surgery, as initial treatment. When survival was broken down by mode of treatment, 25% of patients who received single modality treatment (either surgery or radiation) were DF at two and five years. In contrast, those patients who were treated with bimodal therapy had a DFS of 93% at 2 years and 84% at 5 years. Thus the survival of patients with glassy cell histology treated at our institution with multimodality therapy approximates the survival of similar stage patients with squamous and adenocarcinoma, with a mean follow-up of greater than 5 years. This represents a distinct improvement when compared to national survival statistics. Conclusions: The favorable survival results of this aggressively treated population, supports the belief that multimodality therapy is preferable in patients with glassy cell carcinoma of the cervix even in early stage disease. However, optimal treatment regimens have yet to be determined and is a field for further study.

No significant financial relationships to disclose.
The clinical benefit of cisplatin-doxorubicin combination in heavily pretreated ovarian cancer patients
Authors: Steiner M. , Lavie O. , Leviov M. , Shklar Z. , Rabkin A. , Keren S. , Rubinov R. , Loven D.
Published: March 2020

15052

Background: Cispatin-doxorubicin (Adriamycin) combination (50 mg/m2 each every 3 weeks) was used to treat ovarian cancer patients after failure of various chemotherapy lines. Methods: Eighteen patients were treated. Their mean age was 59 years (median 57.8, 41.3–70.3). They all had post operative first line carboplatin combination therapy (77% taxol containing) and all achieved NED status at end of therapy. They relapsed within 1–74 months from end of carboplatin therapy (median 9.5, mean 14.1). 3/13 patients (23%) were platinum resistant relapsing within less than six months. Second line therapy included carboplatin retreatment in 8/18 patients (44.5%) - (combined with taxol in 5 and as single agent in 3 patients). All patients received Topotecan therapy, 8 as second line, 6 as third line and 4 as forth line of therapy. Cis platin - Adriamycin combination was used as 3rd to 6th line of therapy (median 4th). All patients were in good general condition with normal renal function and had clinical evidence of recurrent disease confirmed by clinical examination and/or CT scan and CA125 level. 6/18 patients (33.3%) had severe symptoms of disease, 6/18 (33.3%) mild to moderate symptoms and 6/18 (33.3%) were asymptomatic. Results: 3–11 cycles of therapy were administered (median 7) using 60–100% of planned dose (median 100). Treatment was generally well tolerated with Grade III toxicity in 4/18 patients (22.2%) - (myelotoxicity in 2 and asthenia in 2 patients). 4/18 patients (22.2%) reported quality of life improvement, 4/18 (22.2%) reported quality of life deterioration and 10/18 (65.6%) stable quality of life during therapy. 13/18 patients (72.2%) benefited from therapy. 5/18 (27.7%) achieved complete response, 3/18 (16.8%) partial response and 5/18 (27.7%) minimal response or disease stabilization. All three platinum resistant patients responded: two achieved complete response and one minimal response. Mean time to progression in all responding patients was 9.4 months (median 8.6, 2.6–16.5). Conclusions: We concluded that Cis-Platin - Adriamycin combination is still effective in heavily pretreated ovarian cancer patients and clinical benefit can be achieved with reasonable toxicity. The combination can be considered an additional treatment option.

No significant financial relationships to disclose.
Biologic behavior for patterns of recurrence and survival in ovarian versus uterine papillary serous carcinoma
Authors: de Souza B.
Published: March 2020

15056

Background: Papillary serous carcinoma of the ovary (OPSC) and uterus (UPSC) are relatively uncommon malignancies with similar histological features. Information for their comparative behavior is lacking, hence a review was done to compare patterns of recurrence, disease-free and overall survival between the 2 groups. Methods: A retrospective review of 352 consecutive patients (pts) at a single institution with ovarian and uterine malignancies from 1991 through 2004 was done. Of these, 48 patients were identified with OPSC (n = 32) and UPSC (n = 16). To control surgeon as a prognostic factor, only pts undergoing surgery by a single surgeon were included. Stages at diagnosis, patterns of recurrence and survival for FIGO stages I-III with a minimum follow-up of 8 months were obtained from tumor registry, hospital and office records. The median follow-up for UPSC was 25 months and for OPSC was 46 months. Stage IV pts were excluded. Results: The mean age for OPSC and UPSC was 64 and 63 years respectively. Of the 32 OPSC pts, 94% had optimal debulking. In the UPSC group 88% had proper staging with lymph node dissection. The pts with OPSC had a mean overall survival of 60 months and a mean disease-free survival of 38 months for all stages combined. The pts with UPSC had a mean overall survival of 51 months and a mean disease-free survival of 40 months for all stages combined. Ten (31%) pts with OPSC had no recurrence. The remaining 22 (69%) pts had a total of 36 recurrences, the most common (17%) being pelvic masses (mean interval of 24 months). In the UPSC group, 9 (56%) had no recurrences. The remaining 7 (44%) had a total of 10 recurrences, the most common (30%) being peritoneal implants (mean interval of 17 months). Conclusions: UPSC is detected at an earlier stage twice as often as OPSC and yet it has lower overall survival. The disease-free interval is comparable, which shows that even after recurrence, the survival for OPSC is longer. Although OPSC and UPSC share similar histological features UPSC behaves more aggressively.

[Table: see text]

No significant financial relationships to disclose.
MGMT methylation in newly-diagnosed glioblastoma multiforme (GBM): From the S0001 phase III study of radiation therapy (RT) and O6-benzylguanine, (O6BG) plus BCNU versus RT and BCNU alone for newly diagnosed GBM
Authors: Blumenthal D. T. , Wade M. , Rankin C. J. , Fitzpatrick F. , Stelzer K. , Sloan A. , Ackerley W. , Rushing E. J.
Published: March 2020

1512

Background: Glioblastoma multiforme (GBM) is a high grade primary brain neoplasm associated with a median survival of less than a year. Historically, one-third of patients seem to benefit from treatment with alkylating chemotherapy. This minority may correspond to a population with decreased levels of active O6-methylguanine- methyltransferase enzyme (MGMT). MGMT repairs tumor DNA damaged by chemotherapy, allowing continued replication after exposure to treatment. Patients with low tumor MGMT activity may be more likely to respond to alkylating treatment. Hypermethylation of the MGMT promoter region leads to decreased transcription of the enzyme and is associated with improved outcome in GBM patients treated with radiation and alkylating chemotherapy. Methods: We studied a patient cohort with newly diagnosed GBM registered on Southwest Oncology Group protocol S0001, a phase III randomized, two arm clinical trial investigating an inhibitor of MGMT (O6-benzylguanine, O6BG). Both groups received standard radiation and BCNU (carmustine). The experimental group additionally received O6BG. We determined polymerase chain reaction (PCR) methylation status of the promoter region of MGMT in 88 patients with adequate tissue samples. In 41 cases, we were able to obtain successful PCR results. Results: 28 of 41 samples (68%) were found to be unmethylated and 13 of 41 (32%, 95% c. i. 18% to 50%) were methylated. Patients with methylated MGMT had a median survival of 12.6 months (95% c.i. of 7.8–15.8 months). Patients with unmethylated MGMT had a median survival of 10.6 months (95% c.i. of 8.7–12.0 months). Median progression-free survivals were 4.5 and 3.1 months respectively, for the methylated and unmethylated groups. Conclusions: This result is consistent with prior studies which showed that approximately two-thirds of patients express MGMT, and accordingly, are resistant to alkylating agents. The subgroup of patients without promoter methylation may be more likely to benefit from treatment with O6BG. Analysis of MGMT promoter methylation status per study treatment group, and correlation with median survival and progression-free survival will be presented.

No significant financial relationships to disclose.
Impact of Karnovsky performance status (KPS) on outcome of elderly patients (pts) with glioblastoma (GBM) and activity of temozolomide (TMZ) as first line therapy: Retrospective analysis of a cohort
Authors: Chinot O. , Barrie M. , Calissi B. , Fuentes S. , Metellus P. , Honore S. , Boucard C. , Loundou A. , Figarella-Branger D. , Dufour H.
Published: March 2020

1515

Background: Due to increasing incidence of GBM in the elderly, prognostic factors and therapeutic strategies need to be considered in this population. Recently radiotherapy has shown survival improvement in patients with KPS ≥ 70 (ANOCEF, EANO 2005), while chemotherapy with TMZ may be considered as a therapeutic option (Chinot at al, Cancer 2003). Methods: We analyzed retrospectively all pts above 70 years old with GBM, who were referred to our institution from May 1998 to October 2004; all responses to TMZ were reviewed. Results: We identified 136 pts registered. Median age was 74 (range 70–87), and 43% had a KPS < 70. Surgery consisted of stereotactic biopsy (SB), 29% ; partial surgery (PS), 12%; and gross total removal (GTR), 29% of pts. Diagnosis was strongly suggested by neuroradiology in 30% of cases. Treatment consisted of TMZ (5 days standard schedule) (group A) as first-line treatment in 89 pts (65%), radiotherapy and/or nitroso-urea based regimens in 40 pts (30%) (group B) and best supportive care in 7 (5%) pts. For the all cohort, median of overall survival (OS) was 7 months (m), strongly impacted by KPS (3.9 vs 8.7 m, p<0.0001 for KPS < 70 and ≥70 respectively) and age (8.2 vs 6.0 m, p<0.007 for age < 75 years vs. ≥ 75). OS was 6.6, 7.3, and 8.4 mos in the case of SB, PS, and GTR respectively and was 5.2 for neuroradiologic diagnosis. In group A, median time to tumour progression (TTP) and OS were 4.7 & 7.3 m. KPS impacted TTP (2.9 vs. 5.1 m, p=0.0002) and OS (4.9 vs. 8.7 m, p<0.0001) for KPS < and ≥ 70 respectively. Response rates (RR) were for 71 pts evaluable 28%; SD 35%; PD 37% associated with an OS of 11.7, 7 and 3.2 m respectively. RR was 34% for histologically proven GBM, vs 22% in cases of neuroradiologic diagnosis. In group B, TTP and OS were 4.3 & 6.7 m respectively. Conclusions: KPS appeared to have a major impact on outcomes in elderly patients with GBM. Future trials designs should take this impact into consideration. TMZ appeared to be effective in elderly patients with newly diagnosed GBM. This alternative approach is currently being tested against RT alone in international trials. Impact of MGMT status in the TMZ population will be presented.

No significant financial relationships to disclose.
11C-Methionine PET to predict survival of glioma patients treated by radiotherapy
Authors: Zhang H. , Tian M. , Zhao C. , Ye X. , Zhan H.
Published: March 2020

1523

Background: The early prediction of glioma prognosis is very important. Amino acid metabolism of glioma is associated with numerous catabolic processes favoring tumor growth. As an essential amino acid, L-methionine plays a central role in the altered metabolism of cancer cells. The aim of this study was to evaluate the prognostic value of PET imaging using 11C-methionine (MET) in patients with gliomas treated by radiotherapy. Methods: MET PET was prospectively performed in 36 patients with gliomas before and within one month after radiotherapy. Tumor MET uptake was measured with the semiquantitative tumor-to-nontumor ratio (T/N ratio). The MET uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analysis. Results: All tumors were identified in the baseline MET PET study. Patients with a baseline T/N ratio of < 4.0 had a significant better survival than patients with a baseline T/N ratio > 4.0 (2-year survival rate: 50.8% versus 0%, P=0.026). Patients with a post radiotherapy ratio of <4.0 had a better survival than that with a post radiotherapy ratio > 4.0 (2-year survival rate: 50.4% versus 0%, P=0.0012). The univariate analysis showed that both baseline and postradiotherapy T/N ratio were statistically significant predictors of patient survival, and postradiotherapy T/N ratio was a significant independent survival predictor in multivariate analysis. Tumors with larger T/N ratio had a significantly poorer prognosis. Conclusions: Baseline MET uptake was a potential survival indicator and postradiotherapy MET uptake was a significant independent predicator in glioma patients treated by radiotherapy. MET PET is a valuable tool in the predication of survival in patients with gliomas treated by radiotherapy.

No significant financial relationships to disclose.
Prognostic model for primary CNS lymphoma (PCNSL): Recursive partitioning analysis (RPA) of the MSKCC PCNSL population
Authors: Abrey L. E. , Benporat L. , Panageas K. S. , Yahalom J. , Deangelis L. M.
Published: March 2020

1531

Background: Increasingly there is a need to develop a simple prognostic score that can be used in the analysis and design of PCNSL studies as well as for clinical management. Recently the IELSG published a 3 group prognostic model incorporating patient age, performance status, serum LDH, location of brain lesions and CSF total protein; however, only 105 of their 378 patients had all of the variables available to develop this score. Methods: We analyzed 338 patients (median age 60; median KPS 70) seen and treated for PCNSL at MSKCC between 1983 and 2003. The median survival was 37 months and median follow up of surviving patients is 35 months. Univariate analysis of potential prognostic factors was performed using the Kaplan Meier product limit method. Significant univariate variables were included in a multivariate analysis using the Cox proportional hazards regression model. Patients were separately analyzed using the IELSG prognostic score. Finally, RPA was employed as an independent method of developing specific prognostic categories. Results: In the univariate analysis, age, hemiparesis, mental status changes, creatinine clearance and KPS were significant predictors of overall survival; in the multivariate model only age and KPS remained as significant predictors. 113 patients had adequate information (all 5 variables) to be analyzed using the IELSG prognostic score; while this correlated significantly with overall survival, the comparison between groups 2 and 3 was not statistically significant (p = 0.10). RPA of all 338 patients identified 3 subgroups: age ≤ 50 (median OS 9.2 y), age > 50 and KPS ≥ 70 (median OS 3.2 y) and age > 50 and KPS < 70 (median OS 1 y) that significantly separated our entire PCNSL population (p < 0.001). Conclusions: The use of RPA allows for easy discrimination of 3 prognostic groups of patients with PCNSL. In contrast to the IELSG score the MSK RPA classification includes information that is readily available on all patients and can be easily incorporated into the analysis or design of clinical research.

No significant financial relationships to disclose.
Although substantial (qol) quality of life problems may occur due to acute and delayed complications of therapy for advanced head & neck squamous cancer, overall long term qol is good/acceptable
Authors: Taneja C. , Somasundar P. , Stager S. , Carroll E. , Wanebo H. J. , Radie-Keane K. , Nadeem O.
Published: March 2020

15510

Background: Patients with locally advanced head and neck squamous cell cancer (HNSCCA) have traditionally been treated with aggressive regimens of concurrent chemo-radiation, or more recently, induction chemotherapy followed by concurrent chemo-radiation, to achieve high rates of tumor control at our institution. Objectives: We initiated a QOL study in patients who were free of tumor and available for long term follow up with a focus on acute & delayed complications and long term QOL observation. Methods: The study included 75 patients with stage III-IV HNSCCA treated with either concurrent chemo-radiation or induction chemotherapy followed by concurrent chemo-radiation at our institution. All patients had completed therapy and were considered free of disease at the time of survey. We were unable to complete the survey in 43 pts largely due to patient access problems or unavailability at time of survey. In the remaining 32 patients, the University of Washington QOL survey could be completed over the telephone. Two pts were excluded due to recent demonstration of recurrence. Additional information regarding acute toxicity during treatment was also recorded. Results: There were 11 women and 19 men with a median duration of follow up of 36 months (range 3–120 months) after completion of treatment. Early complications were associated with gastrostomy tube placement (5 leaks & 6 infections,12/31 patients, 38.7%) and portacath placements (2 deep vein thrombosis requiring port removal and anticoagulation, 6.45%). No patients in this group were still dependent on their gastrostomy tube for nutrition at the time of follow up. Of note, 9% of patients were still smoking and drinking on a regular basis. The composite scores for 9 QOL domains ranged from 370–875, with a median score of 615/900. Major problem issues regarding QOL were associated saliva 11/31 (35.5%), swallowing 10/31 (32.2%), followed by mood 6/31 (19.3%), pain 5/31 (16.12%), chewing 4/31 (12.9%), local pain 5/31 (16.12%) and shoulder problems 5/31 (16.12%). Conclusion: Initial QOL problems in advanced HNSCCA appear related to surgical/chemo therapy related problems, whereas late QOL issues appear primarily related to radiation. Most patients however had a good or acceptable quality of life after treatment for advanced HNSCCA.

No significant financial relationships to disclose.
Activity of irofulven (IROF) combined with capecitabine (CAPE) in patients (pts) with advanced thyroid carcinoma: Phase II international multicenter study (preliminary results)
Authors: Droz J. , Baudin E. , Medvedev V. , Delord J. , Kane M. , Kloos R. , Ringel M. , Kahatt C. , Weems G. , Shah M.
Published: March 2020

15511

Background: IROF, the first compound of the acylfulvene class to enter clinical trials, has demonstrated antitumor activity in a variety of chemoresistant tumors. Currently available chemotherapy offers limited benefit to pts with advanced thyroid cancer. A phase I trial of an IROF/CAPE combination showed confirmed partial responses in 2/4 pts (Alexandre, ASCO 2003). An international multicenter 2-stage, phase II trial was initiated to evaluate the objective response rate (RECIST) in pts with advanced thyroid cancer. Methods: Eligibility criteria included advanced Differentiated, Medullary or Anaplastic (D/M/A) thyroid cancer, ECOG PS 0–2, no benefit from prior I131 and ≤1 prior chemotherapy regimen. Pts received IROF 0.4 mg/kg (30 min IV infusion), days 1 and 15 and CAPE orally 2000 mg/m2 day 1 to 15 every 28 days. Results: As of Dec-05, 23 pts (D/M/A: 14/5/4) have been treated. Pt characteristics are (D/M/A); median age: 60/55/61 years (range 34–74), median PS: 1/1/1; prior chemotherapy in 4/1/2 pts; all had metastatic disease predominantly lung, bone and lymph nodes, with a median of 2/1/3 sites of metastasis. Median number of cycles given was 5/4/1. Efficacy: All pts are evaluable. No objective responses observed to date, SD was observed in 11 (79%)/ 3 (60%)/0 pts with median duration 4.8/5.2/0 months; 2/11 (D) pts with SD had 14% and 19% decreases in tumor size. Safety: Main adverse events were thrombocytopenia (grade [G] 1–2: 24% pts), neutropenia (G1–2: 17%; G3: 4%), nausea (G1–2: 41%), asthenia (G1–2: 41%); 1 pt had G3 asthenia. No pts discontinued due to toxicity. Conclusions: No objective responses were observed in pts with differentiated thyroid cancer treated with IROF/CAPE every 2 weeks, with 79% SD. Tolerance was acceptable and accrual is ongoing in the anaplastic cohort.

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Interstitial high dose rate brachytherapy and cervical dissection the management of recurrent head and neck cancers
Authors: Pellizzon A. C. , Novaes P. , Salvajoli J. , Fogaroli R. , Maia M. , Ferrigno R.
Published: March 2020

15529

Background: The literature is scarce regarding the use of interstitial high dose rate brachytherapy (I-HDR) in this setting, most reports are focused on primary tumors. We performed a retrospective analysis of a single institutional polity of treatment using salvage surgery associated to I-HDR at the Radiation Oncology Departments, Hospital do Cancer A.C. Camargo, São Paulo, Brazil. Methods: All patients with recurrent cervical cancer treated with combination of surgery and I-HDR, with or without the addition a new second course of EBRT, biopsy proven squamous cell carcinoma (SCC), Karnofsky performance status up to 60 and, no evidence of distant metastasis. Patients treated from October, 1994 to June, 2004, were retrospectively selected. Results: Twenty-one patients with median age of 53.5 years (range 31–73) were included in the study. The ratio male to female was 3.2:1 and the follow up time ranged from 6 months to 82 months (median - 36 months). Thirteen (61.9%) had a previous course of irradiation, in whom the median total I-HDR dose was 25.8 Gy, inferior when compared to the median dose of 40.7 Gy given to patients without a previous course of EBRT (p = 0.011), but with no influence in OS (p = 0.9436). The only predictive factor for an improved LFRS and OS was margin status, p = 0.0007 and p = 0.0002, respectively Conclusions: Recurrent HNC should have aggressive salvage procedures as they they are life threatening. Although the number of patients is small, our preliminary results are inspiring, leading to a relative high local control rate with acceptable morbidity,

No significant financial relationships to disclose.
A single institution retrospective analysis of basosquamous carcinoma of the head and neck
Authors: Clement P. , Verheezen J. , Nuyts S. , Vanderpoorten V. , Sciot R.
Published: March 2020

15530

Background: Basosquamous Cell Carcinoma (BSCC) of the larynx, hypopharynx and base of tongue represents 1% of all head and neck tumours. It is considered a more aggressive disease than squamous cell carcinoma, based on higher incidence of advanced stage disease (60% lymph node-involvement and 40% metastases at diagnosis). Therefore, a treatment regimen including chemotherapy is often recommended in addition to surgery and/or radiotherapy in the literature. Methods: We retrospectively analyzed the data of all patients diagnosed with BSCC of the head and neck at the University Hospital of Leuven between 1993 and 2003, and report here the stage at diagnosis, treatment modality, disease evolution, progression free and overall survival. Results: Seven patients where diagnosed with BSCC in the head and neck region. Six patients were male. Three of the tumours were localised in the larynx, two at the base of tongue, and two in the oral cavity. The AJCC stages of disease ranged from I to IVa. Three patients had lymph node involvement at diagnosis. Six patients were treated with surgery in combination with radiotherapy. One patient was treated with cryotherapy before brachytherapy was applied. Five patients have no evidence of disease with a follow up of 4, 5, 6, 10 and 11 years, respectively. One patient died of an unknown cause 18 months after treatment. Only one of the seven patients, developed metastases during follow up. This patient had BSCC of the base of tongue, and was diagnosed with lungmetastases 16 months after surgery and radiotherapy. He was treated with the combination of Doxorubicine, Cisplatin and Fluorouracil. A partial response was confirmed after six cycles. Eight months after the last treatment cycle, there is still no evidence of disease progression. Conclusions: BSCC is a rare tumour of the head and neck. Seven patients were treated at the University hospital of Leuven in the period between 1993 and 2003 with a median progression free and overall survival of more than 5 years. Only one patient developed metastases, and was consequently treated with chemotherapy, inducing a continuing partial remission 8 months after treatment. In contrast to what is reported in the literature we do not confirm a high incidence of metastases at diagnosis nor a high mortality rate.

No significant financial relationships to disclose.
Phase II trial of Gliadel plus O6-benzylguanine (O6-BG) for patients with recurrent glioblastoma multiforme
Authors: Quinn J. A. , Vredenburgh J. J. , Rich J. N. , Reardon D. A. , Desjardins A. , Gururangan S. , Friedman A. H. , Lavin K. , Sathornsumetee S. , Threatt S. , Friedman H. S.
Published: March 2020

1568

Background. The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) which removes chloroethylation or methylation damage from the O6-position of guanine. O6-BG is an AGT substrate that inhibits AGT by suicide inactivation. A previous phase III randomized, placebo-controlled trial has shown that Gliadel wafer significantly prolongs 6-month survival (55.5% for Gliadel vs. 35.6% for placebo) and median survival (28 weeks for Gliadel vs. 20 weeks for placebo) in patients with recurrent glioblastoma multiforme (GBM) (Brem et al 1995). Despite the success of Gliadel in prolonging survival we may be able to improve on this success by depleting AGT. Methods. Thus, we have designed a phase 2 trial where we define the activity and the toxicity of Gliadel in combination with a 5-day infusion of O6-BG in patients with recurrent GBM. In a prior study the O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. In order to guarantee depletion of tumor AGT activity for at least 5 days after Gliadel placement, this O6-BG bolus was repeated on days 3 and 5 while continuing the infusion. Results. To date, 24 patients have been enrolled out of a planned accrual of 50 patients. Seventeen of these patients received prior nitrosourea therapy. The 6-month survival is 68% and the median survival is 36 weeks. The adverse events include the following: 2 episodes of CSF leak (8%), 4 episodes of wound infection at craniotomy site (16%), 5 episodes of grade ≥ 3 seizures (21%) and 3 episodes of hyponatremia (12%). These adverse events were similar in frequency to those seen in patients receiving Gliadel in prior placebo-controlled Gliadel trials. Conclusions. Thus far, this data demonstrates an increase in the efficacy of Gliadel when combined with O6-BG. Twenty-six additional patients will be enrolled for a total accrual of 50 patients.

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