bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic impact of histological response after neoadjuvant chemotherapy in patients with stage IIIC/IV ovarian cancer undergoing complete cytoreductive surgery at the time of interval debulking surgery
Authors: Morice P. , Ferron J. , Rey A. , Zafrani Y. , Uzan C. , Gouy S. , Castaigne D. , Duvillard P. , L'Homme C. , Pautier P.
Published: March 2020

16032

Background: The aim of this study was to evaluate the prognostic impact of histological response at the time of interval debulking surgery (IDS) in patients treated with neoadjuvant chemotherapy (NACT) for unresectable advanced-stage ovarian cancer (ASOC). Methods: A retrospective study was conducted in our institution to select cases fulfilling 3 following inclusion criteria: 1. Patients with unresectable (evaluated in most of them with initial surgery + biopsies) ASOC. All patients had residual disease > 2 cm after such initial surgery; 2. At least 3 courses of platinum + paclitaxel NACT; 3. Patients undergoing after NACT an IDS with absence of macroscopic residual disease at the end of the debulking surgery. IDS was followed by post-operative chemotherapy. Patients were classified into 3 groups according to the histological response (in the peritoneum & nodes) after NACT: group 1: no residual disease in peritoneum; group 2: persistent residual disease but with histological signs of chemoactivity (marked histological changes) and group 3: persistence of at least 1 site with no changes in the tumor (persistence of very active cells). Survival was compared between these 3 groups. Results: Fifty-eight patients treated between 1997 and 2004 fulfilled inclusion criteria (49 had stage IIIC and 9 stage IV disease). Respectively 47 & 11 patients received 3–4 or 5–6 courses of chemotherapy before IDS. Respectively 11, 11 and 36 patients were in groups 1, 2 & 3. The median time of follow-up was 41 months. Three-year overall survival in groups 1, 2 & 3 was respectively: 81%, 39% and 62% (no statistical difference). Three- year event-free survival in groups 1, 2 & 3 was respectively: 46%, 18% and 19% (p=.04 between group 1 versus 2+3). Conclusions: These results suggest that the degree of histological response have a limited impact on the survival of patients when complete debulking surgery is achieved at IDS. The degree of tumor cell viability after initial chemotherapy is not a reliable marker for modifying chemotherapy after debulking surgery in such patients.

No significant financial relationships to disclose.
Role of multivisceral cytoreductive surgery in patients (pts) with recurrent ovarian cancer (ROC): Who will not benefit from radical tumor debulking?
Authors: Koensgen D. , Mustea A. , Weidemann H. , Neumann U. , Neuhaus P. , Pirvulescu C. , Kozo D. , Oskay-Oezcelik G. , Lichtenegger W. , Sehouli J.
Published: March 2020

16036

Background: Despite improvement in surgery and adjuvant chemotherapy most pts with ovarian cancer (OC) experience a relapse within 2 years after first diagnosis. For primary OC a standard concensus on optimal staging and surgical guidelines is established. The role of radical tumor debulking surgery in ROC is not clearly defined. Aim of this study was to analyze clinical parameters for prediction of operability and impact on overall survival in ROC. Methods: Within the framework of the international project “Tumor bank Ovarian Cancer“ (TOC) a systematic prospective surgical and histomorphological tumor documentation for ROC was performed. Results: Between september 2000 and december 2006, 307 multivisceral operations on 254 pts with ROC were performed consecutively in our department. Median age was 55 years (19–83), median follow-up 15 months (1–75). 34.8% of pts experienced first relapse of OC. Overall, 96.3% of pts received a platinum-based first-line chemotherapy, whereas 73.4% were platinum sensitive. In 55% of pts first relapse surgery was performed. In 41.4% of pts complete macroscopic tumor resection was achieved, associated with a significantly better recurrence-free (median 20.6 vs 13.2, p=0.001) and overall survival (median 42 vs 12 months, p<0.001) compared to pts with any postoperative residual tumor. In multivariate analysis, complete tumor resection was associated with the absence of tumor burden in the upper abdomen (p=0.001) and absence of ascites (p=0.05). Prognostic factors for postoperative survival were: tumor resection (0 cm vs > 0 cm, p<0.001), intraoperative volume of ascites (0 ml vs > 0 ml, p=0.006) and response to platinum-based first-line therapy (platinum sensitive vs platinum-resistant, p=0.006). Conclusions: Radical tumor debulking in patients with ROC is associated with a low postoperative morbidity and mortality. Complete mascroscopic tumor resection is correlated with a significant better long-term prognosis and influenced by tumor spread and presence of ascites. Pts with ROC will not benefit from multivisceral cytoreductive surgery in case of platinum resistance to first-line chemotherapy, presence of intraoperative ascites and postoperative residual tumor.

No significant financial relationships to disclose.
Weekly combination chemotherapy of docetaxel and carboplatin and 5-FU in recurrent cervix cancer
Authors: Elkerm Y. M. , Elsaid A. , Elnemr M.
Published: March 2020

16038

Background: The current phase II study assessed docetaxel/carboplatin/5FU given weekly for 24 weeks, for recurrent uterine cervix cancer. Methods: Fourty patients with histologically confirmed, recurrent uterine cervix cancer were enrolled. The patients eligible for this study had histologically confirmed, recurrent uterine cervix cancer. . Patients received weekly docetaxel 20 mg/m2 and carboplatin area under the curve (AUC) 2 weekly with bolus 5FU 500 mg/m2. The response status of the patients was assessed using the common ECOG response criteria. Results: 40 patients were entered in this study. The distribution of intial stage at first presentation was IB, 6 ; IIB, 16; IIIB, 10; IVB, 8. There were 30 squamous cell carcinomas, 6 adenocarcinomas, 4 adenosquamous cell carcinoma. : All patients were evaluable, and completed all planned therapy. The most frequent maximum toxicities during chemotherapy were Grade 2 mucositis with neutopenia. Nonhematological toxicity was generally mild, except for ubiquitous complete alopecia. Responses after 6 months included 6 patients with complete responses, 22 patients with PR and 12 patients with SD. No progression of disease was observed. Conclusions: This regimen was feasible, safe, and particularly well tolerated. Early Phase II outcomes revealed promising activity in patients completing all treatment.

No significant financial relationships to disclose.
Gestational trophoblastic disease: Experience at a tertiary care center from a developing country
Authors: Hariprasad R. , Ganessan K. , Gupta A. , Kumar L. , Kumar S. , Bhatla N. , Kriplani A. , Kochupillai V.
Published: March 2020

16041

Background: We retrospectively analyzed case records of patients diagnosed to have Gestational Trophoblastic Disease (GTD) to determine clinical characteristics, risk groups, treatment outcome, and reproductive function post treatment. Methods: Between Jan 1991 to Dec 2005, 102 patients (mean age: 28.2 years, range 19–50) were diagnosed to have GTD. 35 patients were nulliparous and 8 had prior molar pregnancy. Vaginal bleeding was the most common presenting symptom (77.5%). The antecedent pregnancy was vesicular mole in 50%, abortion - 34.3%, ectopic pregnancy - 4% and term pregnancy in 11.8% patients. The mean value of B hCG was 1225386 mIU/ml. The histopathology (n=85) was complete mole in 30, partial mole - 28, invasive mole- 9, PSTT -1 and choriocarcinoma in 17 patients. 68(66.7%) patients had non-metastatic disease. Sites of metastasis were - lung (38.2%), vagina (11%), brain (8.8%), liver (6.9%) and kidney, Urinary bladder and peritoneum in one patient each. According to modified WHO risk scoring - 78(76.5% had low risk and 24 (23.5%) were high risk. Results: Eighty-seven (85.3%) patients received chemotherapy using methotrexate with leucovorin (n=63), EMA/CO (n=19) and BEP (n=5). 77/87 (89.5%) achieved complete remission (CR) ; the response rate was higher in non-metastatic GTD (p<0.05). Two of 7(28.6%) patients with liver and 5/9 (55,6%) of brain metastasis achieved CR. Two patients had grade III oral mucositis and diarrhoea with methotrexate. One patient died of Methotrexate hypersensitivity. 19 patients received second line chemotherapy using EMA/CO (n=11), EMA/EP (n=2), BEP (n=1), actinomycin-D (n=1) and MAC (methotrexate, actinomycin D and Cyclophosphamide) n=1; 14 patients achieved CR. At a mean follow up of 180 months, 5-year survival for patients with low risk is 100% and that of high risk is 95%. Eight patients had recurrent disease including recurrent molar pregnancy in four. 16 patients had 24 successful deliveries after completion of treatment and 10 of them were primiparae. No fetal abnormalities were found. We did not observe second malignancy or other therapy related sequele. Conclusions: Present study confirms excellent outcome for patients with gestational trophoblastic disease. The potential for childbearing is well maintained.

No significant financial relationships to disclose.
Effect of simultaneous inhibition of MEK and PI3K/Akt pathways on paclitaxel sensitivity in ovarian cancer
Authors: Kigawa J. , Kawaguchi W. , Itamochi H. , Kanamori Y. , Oishi T. , Shimada M. , Sato S. , Sato S. , Terakawa N.
Published: March 2020

16046

Background: Paclitaxel (PTX) is one of the key drugs for ovarian cancer treatment. PTX activates the Raf-mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3’-kinase (PI3K) pathways that lead to cell survival pathways. The purpose of this study was to clarify whether and how the inhibitors of MEK and/or PI3K affect the sensitivity to PTX in ovarian cancer cells. Methods: We treated five ovarian cancer cell lines in combination with PTX and MEK- [PD98059 (PD)] and/or PI3K-inhibitor [LY294002 (LY)] and assessed cell viability, apoptosis, and the expression of phosphorylated (p) MEK and pAkt. The sensitivity of the cell lines to PTX was determined by 3-(4,5- dimethylthiazol-2-yl) -2,5-dyphenyltetrazolium bromide (MTT) assay. The level of protein expression was analyzed by western blot analysis. The drug-induced apoptosis was assessed by Annexin V-FITC staining. Additionally, KOC-2S was injected to intraperitoneal cavity of nude mouse. The effect of combined treatment on the survival in xenograft model was investigated. Results: The levels of pMEK and pAkt protein expression were higher in PTX resistant cell lines (KOC-2S and KFTx) than that in sensitive cell lines (KF, SHIN-3, SK-OV-3). Treatment of PTX induced MEK activation in all five ovarian cancer cell lines. The combination of PTX with either PD or LY led to additive effect on cell growth inhibition. In contrast, synergistic effect was observed in the combination of PTX with PD and LY. Furthermore, apoptotic cells were significantly increased after exposure to PTX and both inhibitors in comparison with other treatment conditions, such as PTX alone, PTX with either PD or LY. The level of pMEK induced by PTX was down-regulated by PD. Interestingly, the level of pAkt was up-regulated by the combination of PTX with PD, which was reduced by LY. Treatment with PTX, PD, and LY prolonged survival in an ovarian cancer xenograft model (p < 0.01). Conclusions: The present study suggests that simultaneous inhibition of MEK and PI3K/Akt pathways enhances the sensitivity to PTX in ovarian cancer. The combination of PTX with MEK- and PI3K-inhibitor may be a new treatment strategy for ovarian cancer.

No significant financial relationships to disclose.
Phase I trial of pegylated liposomal doxorubicin (PLD) and cyclophosphamide (CPM) in patients with relapsed platinum- resistant epithelial ovarian carcinoma (EOC)
Authors: Floquet A. , Cany L. , Dutin J. P. , Jaubert D. , Dupouy C. , Brouste V. , Mathoulin-Pélissier S.
Published: March 2020

16057

Background: Most patients (pts) with EOC recur despite platinum-taxane based first line chemotherapy. Response to second line chemotherapy is limited, and usually related to time between the end of first line treatment and relapse. For early relapses, treatment with non cross resistant drugs or treatment with a different toxicity profile is necessary. Thus, following results of the Gordon study (JCO 2001 Jul 15;19(14):3312–22), a phase I trial of PLD and CPM was planned in patients with EOC who relapsed within 12 months of first line therapy. Methods: This multicenter phase I included 21 pts, PS < 2, age = 18 and = 70, no previous anthracycline, with recurrent EOC (one measurable lesion and/or CA125 elevation RECIST criteria) within 12 months after platinum-taxane first line chemotherapy. Six dose levels were planned : Twenty-one patients were included (3 each at L1, 2, 3 and 4 at L4, 5 and 4 more at L3 ; 18 evaluable patients, 3 excluded due to early PD). No intra patient dose escalation was allowed. Cycles are repeated every 28 days. Toxicity observed on the first 2 cycles. Results: Median age of pts: 59 yrs (22–70). Median platinum-free interval: 6.4 months (0.9–11.7); 71 cycles were administered; 2 DLT NCI G3 were observed at level 4: 1 oesophagitis and 1 stomatitis. No limiting haematological nor skin toxicity was observed. Median follow-up was 25.7 months, 4 surviving pts, 1 with a CR and 3 pts with disease. Conclusions: The combination of CPM and PLD is feasible. The recommended dose for further phase II trial is PLD 40 mg/m2 and CPM 600 mg/m2 every 28 days. [Table: see text]

No significant financial relationships to disclose.
Ovarian adenocarcinoma in teenagers and young adults: A clinical challenge
Authors: Gercovich N. , Carnaval S. , Negro F. , Santillán D. , Abal M. , Morgenfeld E. , Rivarola E. , Deza E. Gil , Gercovich F. G.
Published: March 2020

16070

Background: Ovarian cancer (OC) appears at an average age of 63, and is uncommon in younger patients (pt), with only about 5% being diagnosed below 30 years of age. The aim of this study is to analyze the onset and prognosis of ovarian adenocarcinoma (OA) in teenagers and young adults treated at the IOHM. Methods: From Oct 87 through Nov 06, 467 pt were diagnosed with OC. Twenty six pt (5,35%) were young adults or teenagers. Ten out of the 26 pt had OA, while the other histological types were as follows: 7 pt Germ cell tumors- 5 pt Borderline - 2 pt stromal tumors - 1 pt neuroendocrine - 1 pt undifferentiated. Characteristics of the Population: Median age: 22 years (range 15–29). Symptomatology: 6 pt presented pain and pelvic tumor, two pt malignant ascites, and one skin nodules. Stages: I (4 pt), III (3 pt), IV (2pt), Not registered: 1 pt. Histological Subtype: Serous: 2pt, Endometroid: 1pt, Mucinous: 4 pt. Non-specified adenocarcinoma: 3 pt; Histological Grade: 1: 4pt; 2: 2pt, 3: 3pt. Not registered: 1 pt. Results: All pt were surgically treated (optimal surgical cytoreduction: 5/ 9). All pt received first line chemotherapy based on a Platinum combination. The average follow up time was 58 months (range: 4–162). Five pt are still alive (Median Duration of Survival 78 months (range 12–162) and four of them are free of the disease (Stage I: 3pt and Stage III: 1pt). Conclusions: 1- The OA in teenagers and young adults is uncommon and only stands for 2% of the total ovarian tumors (10/467). 2- In contrast with its adult counterpart, the ascites as an initial symptom was only present in two of our cases. 3-Three out of four stage I pt and one stage III pt are still alive and disease free after 60 months.

No significant financial relationships to disclose.
Prognostic factors in uterine sarcoma: A clinicopathologic and immunohistochemical (IHC) study of 30 cases
Authors: Al-Safi F. , Al Kushi A. , Ameeri S. , Al Merri N.
Published: March 2020

16071

Background: The objective of this study is to examine the prognostic relevance of traditional clinical, pathological and IHC features of uterine sarcoma (US). Methods: The study population consisted of thirty cases of US treated at our institute. Twenty- two cases are HGS (11 leiomyosarcoma, and 11 carcinosarcoma) and eight cases are LGS (5 mullerian adenosarcoma and 3 low grade endometrial stromal sarcoma). Clinical and pathological data including patient's age, parity, menopausal status, tumor cell type, lymphovascular invasion, nuclear grade, stage and mitotic index. Serial sections were immunostained with antibodies for p53, bcl-2, estrogen receptor (ER), Her2 and c-kit. The clinicopathological and IHC features were analysed by using Kaplan-Meier method for constructing survival curves, and log-rank statistic for survival curves comparison. Multivariate analysis was performed using Cox regression modeling. Results: The mean follow-up period of patients is 32 months (range 1- 120). Twelve (55%) patients with HGS died of the disease and none of the LGS group. In the HGS group, stage (p=0.01), myometrial invasion in early stage tumor (p=0.04), and lymphovascular invasion (p=0.043) were significant predicators of patient outcome in univariate analysis. Similarly, tumor cell type, ER, p53 and bcl-2 expression showed statistical significant correlation with tumor-specific survival (p=0.0039, p=0.001, p=0.03, and p=0.04, respectively). ER and bcl-2 expression were associated with better outcome and the opposite for p53 expression. In a multivariate analysis, only the tumor stage and cell type had independent statistical significance (p=0.04, and p=0.035, respectively). Overexpression of p53 and Her2 were observed in 40% and 60% of carcinosracomas respectively and not seen in any of the other tumors. The c-kit immunostain showed focal and weak staining in 40% of carcinosarcoma and only in 33% of leiomyosarcoma. None of LGS had this marker. The ER was expressed only in the LGS group. Conclusions: This study demonstrates that stage and tumor cell type are the most important prognostic indicators of patient outcome in US. IHC markers such as ER, p53, c-kit, and Her2 can be useful ancillary tools to discriminate between HGS and LGS in difficult cases.

No significant financial relationships to disclose.
Retrospective analysis of 105 cases of uterine sarcoma
Authors: Yoney A. , Eskici S. , Eren B. , Salman A. , Unsal M.
Published: March 2020

16079

Background: Currently there is no randomized study based or widely accepted therapeutic modality in uterine sarcomas which are rare tumors forming a heterogeneous group in respect to their pathologic classification. Methods: In our trial, 105 pts. with uterine sarcoma who were referred to our clinic between years 1995–2003 have been retrospectively researched to evaluate the results in this tumor group. 43.8% had Leiomyosarcoma (LMS), 28.6% had Endometrial Stromal Sarcoma (ESS) and 27.6% had a Malign Mullarian Mixed Tumor (MMMT) while the distribution according to the histological subgroups were found to be 58.8% and 41.2% in low + middle grade tumors combined and in high grade tumors respectively. 76.2% had a Total Abdominal Hysterectomy + Bilateral Salphingooverectomy (TAH+BSO), 18.1% had a Total Abdominal Hysterectomy + Bilateral Salphingooverectomy + Lymphadenectomy (TAH+BSO+LND) and 5.7% had a suboptimal surgery as a surgical procedure. 38.1% of the pts. had Radiotherapy (RT), 18.1% had Chemotherapy (CT) and 12.4% had Chemo-radiotherapy (CT+RT) in addition to surgery. Results: The median age of the whole group is 51 (24–87). 55% of our pts. are under 50 years old and 68.5% had an “organ limited disease” ( stages I-II combined). The distant metastases rate is 30% and the local recurrence is 16.2%. All the local recurrences and 90% of the distant metastases have occurred within the first two years. The disease free survival rates at 3 and 5 years are 54.46% and 49.88% ; while the overall survival rates at 3 and 5 years are 54.63% and 51.09% all respectively. The stage is the most important factor effecting on the O.S and 5- year O.S rate is 68.43% in Stage I disease. Conclusions: The aggressive tumor progression pattern and the poor prognosis of uterine sarcomas require adjuvant therapies. The merit of current therapeutic options are still on debate since none of them has proved any specific effects. Planning further multi-center retrospective studies with high number of pts., a more clear description of the prognostic factors and thus the determination of the most appropriate therapeutic option is definitely needed.

No significant financial relationships to disclose.
Radical surgery is not necessary following neoadjuvant chemotherapy in stage III-IV resectable, non-laryngeal head and neck cancer (NLHNC)
Authors: Shultz J. A. , Pameijer C. R. , Ellenhorn J. , Shibata S. , Vora N. , Maghami E. , Paz I. B.
Published: March 2020

16501

Background: Traditionally, following neoadjuvant chemotherapy (NC), head and neck surgeons have insisted in performing radical surgery regardless of the response to NC. This prospective study evaluates the results of conservative surgery following NC in resectable stage III-IV non-laryngeal head and neck cancer (NLHNC). Methods: Between 1993 and 2003, 70 patients with NLHNC were treated with one of the following NC: Cisplatin and 5FU (17.1%); Cisplatin, 5FU, Leucovorin, and Taxotere (58.6%); Cisplatin, 5FU, and Taxol (24.3%). After three courses of NC, patients were reevaluated to determine the need for local therapy. Local excision or biopsy was performed for patients with near-complete pathological response (n-CPR) or patients with a complete pathological response (CPR). Radical surgery was reserved for patients with partial response (PPR). All patients received radiation to the primary and neck. Results: The median follow up was 35 months, median disease-free survival was 33.4 months and 3-year overall survival was 71.4% for the entire group. Thirty-five patients (50.0%) had a complete pathological response (CPR), 11 (15.7%) had a complete clinical response (CCR) and no pathological staging, 5 patients (7.1%) had a n-CPR, and 19 patients (27.1%) had a partial pathological response (PPR). Primary surgery is shown in the following table : At the time of the last follow up, 1/35 (2.9%) patients with CPR had a local recurrence (LR) at the primary and 5/11 (45.5%) patients with CCR and no pathological staging had a LR; in 3/6 (50%) patients with LR the primary was controlled with salvage surgery. Seven of eleven (63.6%) patients with PPR had a LR, only one achieved local control with salvage surgery. Conclusions: Complete pathological response at the primary site is a good predictor of long term local control in NLHNC. Radical surgery, is not necessary in non-laryngeal head and neck cancers following a complete pathological response at the primary site.

[Table: see text]

No significant financial relationships to disclose.
Management of synchronous lung nodules in patients with potentially curable head and neck cancer
Authors: Dowell J. , Ha H.
Published: March 2020

16503

The presence of a solitary pulmonary nodule in patients with otherwise curable head and neck cancer is a complex clinical scenario. We retrospectively reviewed the management of such patients at the Dallas VA Medical Center to determine if our process for selecting patients to treat with curative intent was in fact identifying patients with meaningful survivals. All patients presented at the institutional multimodality head and neck tumor board from 1998 - 2004 were reviewed. This insured more than 24 months follow up for each patient. Included patients had head and neck cancer that was felt to be potentially curable with either surgery and/or radiation or a combination of chemotherapy and radiation. In addition, all had a solitary lung nodule that was biopsy proven and potentially resectable lung cancer. Pretreatment imaging included CT scans of the head and neck and chest. Patients all had adequate renal, pulmonary, and performance status to tolerate planned treatment for their head and neck cancer and thoracotomy for their lung cancer. In all cases, the head and neck cancer was addressed first followed by treatment of the lung cancer. Twelve patients were identified with potentially curable head and neck cancer and a synchronous solitary pulmonary nodule that was biopsy proven lung cancer. Six of these patients were determined to be candidates for aggressive treatment of both cancers. The pathologic stage, survival, and management for the 6 patients were as follows: The synchronous occurrence of potentially curable head and neck and lung cancers was uncommon in our population. Using stringent criteria for selection of patients who might benefit from an aggressive approach to both cancers, we achieved reasonable outcomes with a median survival for the group of 29 months and with 4/6 patients (67%) surviving more than 2 years. Curative intent therapy should be offered to appropriately selected patients.

[Table: see text]

No significant financial relationships to disclose.
First-line docetaxel (Dx) and capecitabine (Cap) in advanced head and neck cancer
Authors: Gil-Negrete A. , Mañe J. M. , Ruiz de Lobera A. , Martinez-Bueno A. , Rubio I. , Fuente N. , Lopez-Vivanco G. , Ancizar N. , Fernandez R. , Sancho A.
Published: March 2020

16505

Background: Dx and Cap are useful drugs in head and neck cancer. Our purpose was to establish the efficacy and safety of this combination in non selected patients (pts) with advanced or metastatic (M1) head and neck cancer. Methods: : Between Apr 2005 and Nov 2006, 33 pts with squamous cell locally advanced or M1 head and neck cancer received the following chemotherapy (Ct) schedule: Dx 75 mg/m2 day 1 and Cap 950 mg/m2/12h days 2–14, every 3 weeks.30 pts (90.9%) had received previous local radiotherapy, 11 of them with concomitant Ct. Results: Mean age was 60 years old (range 46–75). M/F: 32/1. PS 0/1/2: 1/29/3. Location of disease: only local 49%; local and M1 36%; only M1 15% (Main M1 site: lung 76.5%, nodes 11.8%, bone 5.9%, soft tissue 5.9%). Mean number of Ct cycles: 4 (range 1–7). Worst hematologic toxicities per patient G3/G4 (%): neutropenia 6/39; febrile neutropenia 36/0; anemia 3/0; trombopenia 3/3. Non-hematologic toxicities G2/G3 (%): vomiting 3/3; neuropathy 6/0; asthenia 33/6; diarrhea 21/3; mucositis 33/18; nail changes 12/0; hand foot syndrome 3/12. Other events to remark: 4 pts had neumonia (2 toxic deaths), 1 pts had angor and required a different Ct schedule, 2 pts had massive hemorrage (1 exitus). There were 7 pts not evaluable for response (4 not yet evaluated, 1 early death due to massive hemorrage, 1 toxic death due to neumonia, 1 early disphagia). Among the evaluated pts, responses were: 2 CR (7.7%), 10 PR (38.5%), 9 SD (34.6%) and 5 PD (19.2%). Median TTP was 21 weeks (95%CI 17.5 - 24.2). Median OS was 39.8 weeks (95%CI 32.4 - 47.4) by Kaplan-Meier method. Conclusions: This combination appears to be active in pts with advanced or M1 head and neck cancer. Main toxicities were neutropenia, febrile neutropenia, mucositis and asthenia. Global toxicity was important with two toxic deaths documented

No significant financial relationships to disclose.
A phase II study of ARQ 501 in patients with advanced squamous cell carcinoma of the head and neck
Authors: Kawecki A. , Adkins D. R. , Cunningham C. C. , Vokes E. , Yagovane D. M. , Dombal G. , Koralewski P. , Hotko Y. , Vladimirov V.
Published: March 2020

16509

Background: ARQ 501 is a DNA damage checkpoint pathway activator whose effect is to induce selective cell death in cancer cells, independent of the tumor cell's p53 status. Current evidence implicates a rapid and sustained increase of the pro-apoptotic protein E2F-1 by ARQ 501 as the mechanism of action. Cancer cells are selectively affected due to their pre-existing DNA damage. In initial clinical trials, there was evidence of activity in some patients with head and neck cancer and pre-clinical investigations also supported this application. Therefore, a phase 2 trial is warranted in this patient population. Methods: A phase 2 study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck who had received up to 3 prior systemic therapies was initiated to assess overall response rate, progression free survival at six months, and to further characterize safety. Cycles consist of four weekly administrations of ARQ 501 at a dose of 450 mg/m2. Dose escalation is allowed if a patient successfully completed a full cycle of therapy and had no related grade 2 adverse events. Results: 59 patients have been enrolled to date and 47 have received at least one infusion of ARQ 501. Data is available for 34 patients (27M / 7F, median age, 57 years). Of the 47 patients treated, 11 patients did not reach a post baseline assessment (2 deaths, 8 PD prior to week 8 and 1 withdrew consent). Although at the current date, most patients have not reached their first tumor evaluation, 5 have been assessed for response per RECIST at eight weeks and one patient is demonstrating stable disease. The drug has been well tolerated with the most common adverse event being anemia (11% ) with corresponding edema, fatigue (both 5%), dyspnea (4%), and hyperbilirubinemia (2%). Conclusions: ARQ 501 is well tolerated in patients with advanced, recurrent or persistent squamous cell carcinoma of the head and neck. Enrollment is ongoing and further results will be presented.

No significant financial relationships to disclose.
A phase I study of intra-arterial (IA) cisplatin (C) and accelerated fractionation (AF) radiotherapy (RT) for locally advanced head and neck squamous cell carcinoma (HNSCC)
Authors: Yu K. , Yu S. C. , Vlantis A. C. , Kam M. K. , Hui E. P. , King A. , Tsang R. K. , Tse G. M. , Mo F. , Chan A. T.
Published: March 2020

16512

Background: Concurrent IAC and conventional fractionation (CF) RT is an effective treatment for locally advanced HNSCC. AF RT with 2 late concurrent IAC doses may be equally effective since AF RT produces better local tumor control compared with CF RT and late chemotherapy boost may counteract accelerated repopulation of tumor cells. The maximum-tolerated dose (MTD) of IAC given concurrently with AF RT is not known. Methods: A phase I study was conducted in patients with locally advanced stage III/IV HNSCC to determine the MTD of C that was given as 2 selective IA infusions 1 week apart during the last 2 weeks of AF RT (70 Gy/35 fractions/6 weeks) using 6 fractions/week. IV sodium thiosulfate was used to neutralize the systemic toxicity of C. Starting at 100 mg/m2, cohorts of 3 to 6 patients were treated with escalating doses of IAC, in 25 mg/m2 increments, up to the highest level of 200 mg/m2 per infusion. Dose-limiting toxicity (DLT) was defined as the occurrence in 2 patients at a dose level of grade 3 acute mucositis or skin reactions lasting more than 8 weeks after completion of treatment; grade 4 hematologic, infective, metabolic or hearing toxicity; or grade 3 renal, hepatic or neurological toxicity. The MTD was defined as the dose level immediately lower than that resulting in DLT. Results: Ten patients were recruited with a mean age of 56 years. Two patients had stage III; 1, stage IVa; and 7, stage IVb disease. The T-stages were T1 (n = 2), T2 (n = 1), T3 (n = 2), and T4 (n = 5). The N-stages were N0 (n = 2), N1 (n = 1), N2 (n = 4), and N3 (n = 3). Three patients received IAC at a dose level of 100 mg/m2, 3 at 125 mg/m2, and 4 at 150 mg/m2. All patients had the 2 planned doses except one in the lowest dose level who developed grade 3 hyponatremia after the first dose. There was no treatment-related mortality. DLT occurred in 2 patients at the 150 mg/m2 dose level. One of them had grade 4 leukopenia, and the other had grade 3 acute skin reactions lasting 9 weeks after RT. Thus, MTD was 125 mg/m2. At a median follow-up of 24 months, 6 patients remained alive and disease-free. Conclusions: In patients with locally advanced HNSCC, AF RT with 2 doses of late IAC boost was feasible. The MTD of IAC was 125 mg/m2.

No significant financial relationships to disclose.
Gabapentin for the treatment of pain related to radiation-induced mucositis in patients with head and neck cancers treated with intensity modulated radiation therapy (IMRT)
Authors: Bar Ad V. , Both S. , Dutta P. , Quon H.
Published: March 2020

16513

Background: Gabapentin has been reported to effectively treat multiple neuropathic pain syndromes. This retrospective study evaluates the efficacy of gabapentin for the treatment of pain related to radiation induced mucositis, in patients with head and neck cancers, treated with radiation therapy (RT). Methods: This retrospective study includes 30 pts with head and neck cancers, treated with RT, without concomitant or induction chemotherapy. IMRT planning was performed using a concomitant boost technique with a median dose of 54 Gy, 63 Gy, and 66 Gy delivered to the low risk clinical tumor volume (CTV), high risk CTV and boost target volume, respectively, using 30- 34 fractions. The dose of gabapentin was gradually increased starting on the second week of RT from 600 mg/day to the dose of 2700 mg/d over the course of one week. Narcotic pain medication (Roxicodone) was prescribed as needed. Results: 26 (86%) pts required no pain medication during the first two weeks of RT, despite the presence of grade 1 and/or 2 mucositis in 24 of them. During the third and fourth weeks of RT, 28 (93%) pts were treated with a median dose of 2700 mg/day of gabapentin, with only 3 (10%) pts requiring low dose narcotic pain medication, 15–30 mg/day of Roxicodone, added to gabapentin for adequate pain control, despite grade 2 or higher mucositis in 22 pts. During weeks 5 and 6, 28 (93%) pts continued to be treated with a median dose of 2700 mg/day of gabapentin with only 10 (35%) pts requiring 15–40 mg/day of Roxicodone, in addition to gabapentin for pain control, despite the presence of grade 2 or higher mucositis in 23 pts. Only 3% of the pts in this group had delay in RT delivery. Gabapentin was well tolerated with only 13% of pts experiencing mild side effects (somnolence, nausea, or vomiting), which were managed with reducing the dose or changing the dosing schedule. Conclusions: Gabapentin is effective and well-tolerated for the treatment of mucositis-induced pain related to radiation treatment in patients with head and neck cancers, treated with IMRT. We further demonstrate that the use of gabapentin at doses of 2700 mg per day can reduce or eliminate the need for narcotic pain medication.

No significant financial relationships to disclose.
Phase I trial of pemetrexed (P) in combination with cetuximab (C) and concurrent radiotherapy (RT) in patients (pts) with head and neck cancer (HNC)
Authors: Smith R. , Karamouzis M. V. , Heron D. E. , Ferris R. L. , Lai S. Y. , Kim S. , Boyer T. , Grandis J. R. , Johnson J. T. , Argiris A.
Published: March 2020

16516

Background: P is a multitargeted antifolate that has demonstrated activity in HNC and radiosensitizing properties in animal models. C is a chimeric IgG1 monoclonal antibody directed against the epidermal growth factor receptor that has increased the survival of pts with stage III/IV HNC when added to RT. We conducted a phase I study to evaluate the dose-limiting toxicities (DLT) and maximum tolerated dose of P when combined with standard RT and C. Methods: Pts with high-risk HNC were enrolled and evaluated separately in 2 cohorts: pts with no prior head and neck RT (cohort A) and previously irradiated pts (cohort B). A loading dose of C 400 mg/m2 was given intravenously 7 days prior to starting RT followed by 250 mg/m2 weekly throughout RT. RT was given 2 Gy/day to a total dose of 70 Gy (cohort A) or 60–66 Gy (cohort B). P was administered intravenously on days 1 and 22 (and day 43 if >60 Gy was delivered) according to the following design: Starting dose level (0)-350 mg/m2, dose level (-1)-200 mg/m2, dose level (+1)-500 mg/m2. Additional pts could be treated at a lower dose level while other pts were being evaluated at a higher dose level. Results: 18 pts have been enrolled (A: 14; B:4). 2 pts in cohort A were not evaluable and replaced (1 pt was noncompliant due to transportation issues and 1 pt had sudden death attributable to aspiration). Histological types: squamous cell (13), undifferentiated (1), medullary thyroid (1), adenoid cystic (1), and adenosquamous carcinomas (2). In cohort A, 2 DLT (both neutropenic fever with ANC <500) occurred: 1/6 at dose level 0 and 1/6 at dose level -1. In cohort B, no DLT has occurred: 0/3 pts at dose level 0 and 0/1 pts at dose level +1. There were no grade (G) 4 non- hematologic toxicities. Other serious toxicities included: neutropenic fever (NF) with ANC <1000 (n=1), G 3/4 neutropenia (n=3/n=4), G 3 dysphagia (n=5), G 3 dermatitis (n=3), G 3 mucositis (n=4), G 3 fatigue (n=1), and G 3 anemia (n=1). Due to the development of 3 cases of NF in cohort A the protocol was amended and prophylactic antibiotics were added. Conclusions: The addition of P to RT and C was feasible in pts with or without a history prior RT. Neutropenia and in-field toxicities were predominant but manageable. Pts are currently being treated at dose level +1 (P 500 mg/m2).

No significant financial relationships to disclose.
Retrospective analysis of surgical resection after induction chemotherapy for patients with T4b squamous cell head and neck cancer
Authors: Rivera F. , Vega-Villegas M. E. , López C. , López-Brea M. F. , Rodriguez-Iglesias J. , Rubio A. , del Valle A. , García- Reija M. F. , García-Montesinos B. , Sanz-Ortiz J.
Published: March 2020

16517

Background: Although standard treatment of patients with T4b Squamous Cell Head and Neck Cancer (T4b-SCHNC) for the last decade has been concomitant Chemo-Radiotherapy (CT-RT), recent Phase III trials with new Induction Chemotherapy (IC) regimens suggest that IC could also play a role in this setting. The value of adding surgery of the residual mass after IC and before RT if the resection is technically feasible is not clear in this context. Methods: We present the results of a retrospective analysis focused on this topic. Results: Between 1984 and 2001, 113 patients (pts) with T4b-SCHNC were treated at our institution with platin-based IC. Four pts dead during IC and 57 pts achieved a complete or a >90% partial response at primary and proceeded to definitive RT (or concomitant CT/RT). In the other 52 pts, surgical resection was reconsidered after IC and before RT and in 13 of them this surgery was performed: in 7 pts (6 had PR and 1 minor response after IC) the resection was R1, all these patients had loco-regional progression (2 of them also developed systemic metastases) and median OS after surgery was 21 months with no patient alive at 48 months; In the other 6 pts (3 had a PR and 3 had minor response after IC) an R0 resection was performed: 3 of these pts had loco-regional relapses (1 of them also developed systemic metastases) and the other 3 pts remain alive and disease free 56, 62 and 72 months after surgery. OS of the 52 pts that achieved less than a 90% partial response at primary with IC, was equivalent for those no resected after IC pts and for R1 resected pts (actuarial 5 year OS 8% vs 0%, lrk, p=0,74) but a statistically significant improvement in OS was observed when an R0 resection was obtained after IC (actuarial 5 years OS 50%, lrk, p=0,02).Conclusions: R0 resections after IC and before RT could improve OS in pts with T4b-SCHNC that obtain less than a 90%PR at primary after IC. R1 resection appears to have no value in this setting. This approach should be studied in properly designed prospective clinical trials.

No significant financial relationships to disclose.
Malignant salivary gland tumors: A large single-institutional series evaluating long-term outcome
Authors: Limaye S. , Dulala R. , Roy R. , Thomas A. , Janson D. , Fantasia J. , Mehrotra B.
Published: March 2020

16523

Background: Malignant salivary gland tumors comprise 3 to 6% of Head and Neck cancers. Long term survival data for salivary gland tumors are lacking. We undertook an analysis of all such patients treated at our institution over a 15 yr period. Methods: IRB approval was obtained for this retrospective analysis. Tumor registry data were reviewed for all adult patients diagnosed with salivary gland malignancies for the years 1990 - 2005. Age, Gender, Stage, histology, treatment modalities and survival data were recorded. Results: 200 patients were identified. Median age was 64 yrs (59–69). M:F ratio was 1:1.1 (M: 96; F: 104). Histology and stages: ( Table 1 )Mucoepidermoid Carcinoma (n=50), Adenoid Cystic Carcinoma (n=21), Acinar Cell Carcinoma (n=19), Adenocarcinoma (n=22; Stages: I= 7, II= 4, III= 3, IV= 8), Squamous (n= 12; Stages: I= 1, II= 3, III= 3, IV=5), Poorly Differentiated Carcinoma(n=10), Epithelial Myoepithelial Carcinoma (n=7), Malignant Mixed Carcinoma (n=4), Malignant Myoepithelioma (n=2), Carcinoma in Pleomorphic Adenoma (n=2) and Others (n=15). Hodgkin's and NHL (n=36).Treatment modalities: Surgery (S): n=88 (44%), Radiotherapy (RT): n=6 (3%); Chemotherapy (CT): n=6 (3%); S+RT: n =76(38%); S+CT: n=8 (4%); RT+CT: n =2(1%); S+RT+CT: n =4 (2%). Observation only : n=10(5%). Survival data (Med. survival and 5 yr OS respectively) for all histologies excluding lymphomas are: Stage I - 84 mos,93%; II - 93 mos,85%; III - 39 mos,60 %; IV - 24 mos, 40%. Survival data (Med survival and 5 yr OS) for lymphomas: Stage I - 55 mos,85%; II - 20 mos, 0%; III - 100 mos, 100%; IV- 48 mos, 25%. Median survival of all histology types excluding lymphoma by treatment: S=55 mos, S+RT= 60 mos, S+ CT= 56 mos, RT= 53 mos, RT+CT=15 mos, CT= 24 mos. Conclusions: This large series provides long term outcome data for a relatively rare group of HNCs. Long term survival is noted in several histological sub-types even in the setting of advanced disease. These data should help further define the natural history and biological behaviors of these tumors.

[Table: see text]

No significant financial relationships to disclose.
Oxaliplatin and capecitabine (XELOX) as first-line therapy for metastatic or relapsed squamous cell carcinoma of the head and neck
Authors: Silva O. E. , Tolba K. , Farfan N. , Karr M. , Calfa C. , Raez L. E.
Published: March 2020

16524

Background: Prognosis is very poor when patients with head and neck (H/N) squamous cell carcinomas (SQCC) present with systemic metastasis or disease relapse after primary therapy. (Survival less than 6 months despite palliative therapy). Capecitabine (Xe) is a rationally designed, oral, tumor-selective fluoropyrimidine that mimics continuous 5-FU infusion. Oxaliplatin (Ox) is an alkylating agent that is not generally cross-resistant to cisplatin or carboplatin, and it was shown to be more effective that cisplatin and with increase the antitumor activity of 5-FU in tumor models. Methods: The objective of this study was to determine the safety and efficacy of this new combination (XELOX) for pts with H/N SQCC. Based in two phase I studies with solid tumors we choose the combination of Ox: 130mg/m2 IV day 1, and Xe: 850 mg/m2 PO BID day 2 to 15 every 21 days. Pts were treated until there is disease progression or received a maximum of 6 cycles. All pts had metastatic or relapsed H/N SQCC and they had not received chemotherapy yet for their metastatic or relapsed disease. Results: We have enrolled 16 pts. The enrollment was slower than predicted because several patients that were elegible were not enrolled because they were not able to swallow Xe due to the presence of feeding tubes. The median age was 61 years (range 46–78), most of them were males (10/16), smokers (13/16), whites (13/16), with ECOG PS 1 (11/16), and with Hispanic heritage (10/16). Eleven of them had metastasis to the lungs already and most of the pts had already received chemotherapy (9/16) or radiation therapy (14/16) during the initial therapy. Two pts withdraw consent and were not treated. From the 14 eligible pts to asses response we had 2 partial responses and 6 disease stabilizations. From 47 cycles administered we have seen few grade ¾ adverse (all of them less 10%) events including: leucopenia, hyponatremia, hoarseness, hyperglycemia, depression, and respiratory failure. Two pts reported grade 3 tumor pain. Conclusion: This study shows that the XELOX combination is probably safe and might be effective in the palliative therapy of patients with relapsed or metastatic SQCC of the H/N with these poor prognostic features.

No significant financial relationships to disclose.
Effects of intralesional 32P in refractory patients with head and neck tumors
Authors: Dempke W. C. , Gunawardena B. , Hesselt B. , Linke R. , Alimi K. A.
Published: March 2020

16529

Background: The clinical outcome of refractory head and neck cancer patients remains poor despite novel treatment strategies. In this pilot study we investigated the efficacy of intratumoral injection of 32-P chromic phosphate in 14 patients with refractory head and neck cancers in terms of response rates and overall survival. Methods: Fourteen patients (median age: 59 years) with either cytostatic drug-resistant tumors or tumors known to be primarily chemotherapy-resistant were entered into the study. After sonographic determination of the tumor volume, 32-P chromic phosphate (74–555 MBq) was injected into the central part of the tumor under sonographic guidance. Follow-up investigations included serial scintigraphy, sonographic examinations, and hematologic studies. Results: Injection of 32-P chromic phosphate into refractory head and neck tumors resulted in remarkable regression. The median survival of all patients was 7.8 months (range: 4–16). The response rate (partial response) was 57% (8 patients). However, 6 patients (43%) did not respond to the treatment. In 3 patients thrombocytopenia (grade I/II) was observed, but no other side effects were apparent. Significant pathologic and anatomic changes within the tumor tissue were demonstrated. In all cases examined, formation of a cyst within the area of central activity, surrounded by a centrifugal necrotic ring and a marginal fibrotic structure, was found. Conclusions: Lack of persistent systemic or local side effects, as well as noteworthy efficacy, are properties of this novel regional treatment modality with 32-P chromic phosphate. This modality deserves consideration for further clinical trials.

No significant financial relationships to disclose.