Post-surgery Radiotherapy Research Articles

P06.09.B TRIAL IN PROGRESS: PHASE 1 DOSE-FINDING STUDY TO EVALUATE SAFETY AND TOLERABILITY OF CVGBM IN PATIENTS WITH NEWLY DIAGNOSED AND SURGICALLY RESECTED MGMT-UNMETHYLATED GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma (GBM) is characterized by a low mutational burden limiting the number of neoantigen targets for cancer vaccines. Vaccination against tumor-associated antigens over-presented via MHC class I and II in GBM is an alternative that has shown promise in previous trials. One cancer vaccine containing peptides presented by HLA-A*02-01 (class I) and some DR alleles (class II), showed evidence of peripheral vaccine-induced immune response against these peptides in patients with GBM. Our study will assess the safety and immunogenicity of the messenger ribonucleic acid (mRNA)-based multiepitope vaccine CV-GBM, an investigational therapeutic mRNA vaccine, encoding eight of these peptides that have demonstrated immunogenicity as peptide vaccines. CV-GBM consists of a mRNA with unmodified nucleotides formulated with lipid nanoparticles. MATERIAL AND METHODS CV-GBLM-001 is a first-in-human, open-label, international, dose-escalation phase 1 trial. HLA-A*02:01-positive patients with newly diagnosed MGMT-unmethylated GBM (CNS WHO Grade 4), including IDH-wildtype astrocytoma with a molecular signature of unmethylated MGMT-GBM who have had a gross total or partial resection and who completed post-surgery radiotherapy with or without chemotherapy, are eligible to receive CVGBM. The trial comprises a dose-escalation part (Part A) followed by a dose-expansion part (Part B). In Part A, the starting dose is 12 µg mRNA, which may be escalated to 25 µg, 50 µg and 100 µg, with 3 to 6 patients per dose level. Dose escalation will be guided by a Bayesian logistic regression model. Patients will receive 7 doses of CVGBM by intramuscular injection on Days 1, 8, 15, 29, 43, 57, and 71, followed by 6 optional doses at 6-week intervals, up to 1 year after the first dose or until disease progression or intolerable toxicity. An independent Data and Safety Monitoring Board will recommend the dose for expansion in Part B in which about 20 patients will be enrolled. Biomarkers and vaccine-induced innate and adaptive immunogenicity, including, but not limited to, systemically induced cytokines and chemokines and antigen-specific CD4+ and CD8+ T cells, will be monitored in the blood, and optionally in vaccine-draining lymph nodes and relapsed tumor. In addition to the primary safety objectives, secondary objectives of efficacy (progression-free survival, overall survival) and patient-reported quality of life outcomes will be assessed. Trial sponsor: CureVac SE, Germany.

Clinicopathologic Profile, Management and Outcome of Sinonasal Ameloblastoma-A Systematic Review.

Sinonasal ameloblastoma (SNA) is considered to be a subtype of ameloblastoma. It differs from gnathic ameloblastoma in terms of clinicopathologic features, management and prognosis. Thus, the objective of the present review was to study the complications, survival, recurrence rate and outcomes following the management of SNA. The electronic search process was conducted on PubMed-Medline, Embase, and Scopus. Google Scholar was used to search grey literature. Quality assessment of the case reports (CR) and case series (CS) was done based on CARE guidelines. The initial search resulted in 2111 articles. 15 studies (13 CR and 2 CS) were found to meet the eligibility criteria. The majority of the studies described histological features of SNA, which were consistent with ameloblastomas of gnathic origin. There were no SNA-related deaths reported in the included studies. Five studies described endoscopic surgeries to remove SNAs, and three SNAs were treated with post-surgery radiotherapy. Data from included studies suggest that sinonasal ameloblastomas are histologically similar to gnathic ameloblastomas, but their clinical presentation is different. They may cause complete or partial obstruction of the nasal cavity and the sinus. They appear to affect an older demographic, and their resection may be accompanied by the excision of a large portion of the maxilla, necessitating maxillofacial prosthetic rehabilitation.

Vulval Lymphangiectasia Post-radiotherapy in Cervical Cancer

Cutaneous lymphangiectasia is a benign cutaneous disorder of dilatation of the dermal and subcutaneous lymphatic channels, which occurs rarely on the vulva. It can be congenital or acquired developing secondary to tuberculosis, surgery, and radiotherapy. We report the case of a 58-year-old female patient who gives a history of cervical cancer, for which she underwent hysterectomy and postsurgery radiotherapy 3 years back, now presenting with multiple lumps over the vulva, which discharged clear fluid for 1 year. Acquired vulval lymphangiectasia develops 7–15 years postradiotherapy or surgery commonly, while in our case, it developed earlier. On local examination, there were multiple shiny translucent and hyperpigmented “frog-spawn like” vesicles and papules present over the lower midabdomen, mons pubis, and labia majora. Diagnosis of vulval lymphangiectasia was made on the clinical findings and biopsy. Biopsy revealed dilated lymphatic channels in the superficial and deep dermis. CO2 laser treatment was done for the patient.

Late-onset retinoblastoma camouflaged with proven chronic uveitis: A case report

A rare case of a 16year old female, diagnosed elsewhere as chronic uveitis in the left eye positive antinuclear antibodies and Anti-SSA antibodies, treated with steroids and referred for cyclocryotherapy for a painful blind eye. On examination, the patient denied perception of light. There was proptosis, limitation of extraocular movements and corneal melting with no view of the posterior segment. Ultrasound B scan showed dense vitritis with doubtful specks of calcification. Magnetic resonance imaging revealed a soft tissue mass obliterating the vitreous and anterior chamber with retroscleral extension and involvement of the optic nerve. Extended enucleation was performed under General anaesthesia. Histopathological examination confirmed a well differentiated retinoblastoma with extrascleral and optic nerve involvement. Metastatic work up was normal. Intravenous Chemotherapy and post surgery radiotherapy to the socket was advised for further management. Late onset retinoblastoma mimicking ocular inflammation with positive antibody serology is rare and the report shows the need for imaging in refractory uveitis.

Recurrence Features and Factors influencing Post-relapse Survival in Early-stage Endometrial Cancer after Adjuvant Radiotherapy.

Purpose: To evaluate the recurrent patterns and effect of clinicopathological factors on survival after recurrence (R-OS) in early stage endometrial cancer (EC).Methods: Patients with FIGO stage I-II EC, who underwent post-surgery radiotherapy (RT) at our institution between 2000 and 2017, were enrolled. First recurrent patterns, overall survival (OS), and R-OS were evaluated. Univariate and multivariate analyses (MVA) were used to evaluate factors associated with R-OS.Results: 756 patients were analyzed including 510 patients who received vaginal brachytherapy (VBT) and 246 patients who received external beam radiotherapy (EBRT) ± VBT, of whom 66 patients experienced recurrence, including 21 locoregional relapses and 45 distant metastases. Outside RT field recurrence predominated intra-RT field recurrence (106 versus 10 lesions). The 5-year OS rates for patients with and without recurrence were 62.2% and 98.2%, respectively (p<0.001). Among patients who underwent previous VBT, the 5-year OS rates were 61.1%, 92.3%, and 99.1% for distant metastasis, locoregional relapse, and non-recurrence, respectively (p<0.001); among patients who received EBRT ± VBT, the 5-year OS rates were 51.4%, 50.0%, and 98.3%, respectively (p<0.001).On Cox MVA of R-OS for locoregional recurrence patients, para-aortic lymph node metastasis was associated with poorer R-OS (hazard ratio [HR] 10.047, p=0.039), and salvage RT was superior to other therapies (HR 0.06, p=0.026). On Cox MVA of R-OS for distant metastasis, patients with brain metastasis (p=0.041) had the worst R-OS and patients benefited most from combined therapy (HR 0.02, p=0.001).Conclusion: Recurrent patterns were dominated by outside RT field and distant metastasis for early-stage ECs after adjuvant RT. The modality of prior RT had an impact on the choice of salvage therapy. RT could still be an effective salvage treatment for patients who develop locoregional recurrence. Patients with distant metastasis may benefit from combined therapies.

Use of Intraoperative Frozen Section in the Surgical Management of Patients with Nonmelanoma Skin Cancer.

Background Intraoperative frozen section (IFS) is often utilised in the surgical treatment of nonmelanocytic skin cancer (NMSC) in sensitive facial regions when Mohs micrographic surgery (MMS) is not available. Objective To compare the outcome of NMSC patients with excision performed with and without IFS. Materials and Methods A retrospective, single-centre study was performed on all patients who had undergone resection of NMSC with and without IFS control at the National University Hospital (NUH) from 2010 to 2015. Results 116 patients were recruited, of which 86 had IFS and 30 did not. The complete excision rate of patients with IFS was higher at 87.2% (p=0.0194), need for secondary operation was lower at 1.2% (p=0.005), and need for postsurgery radiotherapy or chemotherapy was lower at 1.2% (p=0.001). The average duration of surgery in patients who underwent IFS was 95.4 minutes compared to 70.1 minutes in cases which did not undergo IFS. Conclusion Our study showed an increased complete excision rate and reduced need for secondary surgeries and adjuvant therapy in patients with IFS. However, a longer operative duration was required. Use of IFS may be useful in patients with NMSC lesions in sensitive regions requiring complex reconstruction after tumour excision.

MiR-200c-based metabolic modulation in glioblastoma cells as a strategy to overcome tumor chemoresistance.

Glioblastoma (GB) is the most aggressive and common form of primary brain tumor characterized by fast proliferation, high invasion and resistance to current standard treatment. The average survival rate post-diagnosis is 14.6months, despite the aggressive standard post-surgery radiotherapy concomitant with chemotherapy with temozolomide (TMZ). Currently, efforts are being endowed to develop new and more efficient therapeutic approaches capable to overcome chemoresistance, inhibit tumor progression and improve overall patient survival rate. Abnormal microRNA (miRNA) expression has been correlated with chemoresistance, proliferation and resistance to apoptosis, which result from their master regulatory role of gene expression. Altered cell metabolism, favoring glycolysis, was identified as an emerging cancer hallmark and has been described in GB, thus offering a new target for innovative GB therapies. In this work, we hypothesized that a gene therapy-based strategy consisting of the overexpression of a miRNA downregulated in GB and predicted to target crucial metabolic enzymes might promote a shift of GB cell metabolism, decreasing the glycolytic dependence of tumor cells and contributing to their sensitization to chemotherapy with TMZ. The increase of miR-200c levels in DBTRG cells resulted in downregulation of messenger RNA of enzymes involved in bioenergetics pathways and impaired cell metabolism and mobility. In addition, miR-200c overexpression prior to DBTRG cell exposure to TMZ resulted in cell cycle arrest. Overall, our results show that miR-200c overexpression could offer a way to overcome chemoresistance developed by GB cells in response to current standard chemotherapy, providing an improvement to current GB standard treatment, with benefit for patient outcome.

Squamous cell carcinoma arising from inverted Schneiderian papilloma: a case report

BackgroundSinonasal inverted papilloma or Schneiderian papilloma is a rare benign tumor of paranasal sinuses and nasal cavities. It can cause bone remodeling and has a significant malignant potential. Hence, it is very important to diagnose and treat the tumor at the earliest. Recurrence can occur even after surgical extensive resection.Case presentationThis case report highlights a case of a 36-year-old male patient who presented with right-sided reduced vision, nasal blockage, headache, and occasional blood-tinged nasal discharge.CT scan of paranasal sinuses revealed chronic sinonasal polyposis with secondary fungal colonization. MRI of the brain with orbit and PNS was suspicious for aggressive neoplastic disease with encasement of the cavernous sinuses and involvement of orbital fissure. The patient was operated for extended functional endoscopic sinus surgery. Histopathology revealed moderately differentiated invasive squamous cell carcinoma associated with Schneiderian (inverted) papilloma. Post-operatively, the patient received radiation for 4 weeks. Post-operative check nasal endoscopy was done 3 and 6 months after completion of radiotherapy which showed no evidence of recurrent disease with good healing and mucosalization of all the sinuses.ConclusionsSinonasal inverted papilloma, though a benign tumor, may turn malignant. Diagnosis is based on radiological investigations (in order to know the extent of the disease) and biopsy (to check if it is benign or additional malignancy present). Staging of the tumor helps in outlining the treatment protocol in each case. Post-surgery radiotherapy is indicated in cases where there is malignancy or complete resection of the tumor cannot be achieved. Meticulous follow-up of the post-operative patients is vital to check for recurrence.

Cervical cancer patterns of care in Italy: A radiation oncology survey of MITO and AIRO GYN groups

Large heterogeneity in therapeutic approaches to cervical cancer (CC) patients has been registered worldwide; a national survey exploring practice settings and equipments in CC treatment was distributed to radiation oncologists. Questionnaires were compiled in 90 of 194 Centers (compliance: 46.3 %). Most of respondents reported the presence of multidisciplinary tumor board, and modern equipments/techniques; 55.5 % of centers reported >1 brachytherapy (BT) equipment, thus implying the need to refer their patients outside for the remaining centers. Post-surgery radiotherapy was performed in 96.7 % of early CC (ECC) cases with pathological high risk factors. Exclusive chemoradiation with concomitant platinum schedules was referred to be used by 84.4 % of centers in locally advanced CC. Alternative options were reported with a range between 4.4 and 28.9 %. The present survey reports a broad spectrum of therapeutic options for CC in Italy. Availability and use of modern techniques is quite diffuse, but the distribution of BT resources and skills remains a challenge.

On high-risk, low-grade glioma: What distinguishes high from low?

The distinction between high‐risk and low‐risk patients with low‐grade glioma is far from clear. yet this criterion is used to select patients for immediate postsurgery radiotherapy and chemotherapy.

SIS-ECM Laden with GMSC-Derived Exosomes Promote Taste Bud Regeneration

Oral cancer has a high annual incidence rate all over the world, and the tongue is the most frequently affected anatomic structure. The current standard care is ablative surgery of malignant neoplasm, followed by tongue reconstruction with free flap. However, such reconstructive modalities with postsurgery radiotherapy or chemotherapy can hardly support the functional recovery of the tongue—particularly, functional taste bud regeneration—in reconstructed areas, thus seriously affecting patients’ prognosis and life quality. Using a critical-sized tongue defect model in rats, we show that combinatory transplantation of small intestinal submucosa–extracellular matrix (SIS-ECM) with gingival mesenchymal stem cells (GMSCs) or their derivative exosomes promoted tongue lingual papillae recovery and taste bud regeneration as evidenced by increased expression of CK14, CK8, and markers for type I, II, and III taste bud cells (NTPdase 2, PLC-β2, and AADC, respectively). In addition, our results indicate that GMSCs or their derivative exosomes could increase BDNF expression, a growth factor that plays an important role in the proliferation and differentiation of epithelial basal progenitor cells into taste bud cells. Meanwhile, we showed an elevated expression level of Shh—which is essential for development, homeostasis, and maintenance of the taste bud organ—in wounded areas of the tongue among animals treated with GMSC/SIS-ECM or exosome/SIS-ECM as compared with SIS-ECM control. Moreover, our data show that GMSCs or their derivative exosomes promoted innervation of regenerated taste buds, as evidenced by elevated expressions of neurofilament and P2X3 at the injury areas. Together, our findings indicate that GMSC/SIS-ECM and exosome/SIS-ECM constructs can facilitate taste bud regeneration and reinnervation with promising potential application in postsurgery tongue reconstruction of patients with tongue cancer.

Soft-tissue sarcomas in adults: Consultation analysis.

e23572 Background: Soft-tissue sarcomas are a rare heterogeneous group of malignant tumors. They originate in the mesodermal leaf and affect the soft tissues (fatty tissue, muscle, tendons, blood vessels, nerves and deep tissues of the skin). It is a heterogeneous disease in its histology with more than 50 subtypes. Because of the infrequent occurrence of the disease, its management is case by case by a interdisciplinary team. Methods: The present study is descriptive. It includes all patients older than 17 years with a diagnosis of soft tissue sarcoma who attended consultation in the Bone Tumors, Skin and Soft Tissue Unit at the Institute of Oncology ¨Dr. Heriberto Pieter¨ from September 2016 to April 2017. Patients with Kaposi sarcomas, GIST, Rhabdomyosarcomas, Ewing Tumors and patients younger than 17 years were excluded. The data obtained was processed in Epi Info and the results presented in graphs and tables. Results: From the sample of patients, 94 corresponded to adult soft tissue sarcomas, 75 were follow-up consultations (79.79%) and 19 first-time consultations (20.21%). The most frequent age of presentation was 41-50 years (23.40%), 51-60 years (20.21%) and 31-40 years (19.15%). The most affected gender was female (59.57%). The most frequent anatomic location was the extremities (55.32%), trunk and pelvis (15.96%) and head and neck (13.83%). Clinical stage III was the most frequent (37.23%), IA and IB were respectively 20.21% and 13.83%. The most frequent sarcomas were fibrous tissue (36.11%), unknown histogenesis (20.21%), and adipose tissue (19.16%). From the total sample, 71 patients (37.77%) underwent wide resection, 14 patients (7.45%) amputation, and 3 patients (1.60%) metastasis resection. Furthermore, 55.3% of patients received chemotherapy. Of these, 56.89% was adjuvant, 10.34% was neoadjuvant and 32.75% of cases were metastatic and / or unresectable disease. Total survival was 87%, with 58.5% of patients alive and disease-free, and 34.0% alive with disease. Conclusions: Based on our analysis, we see that treatment priority should focus on clinical stage III. Survival rates could be improved by a multidisciplinary approach including neoadjuvant chemotherapy, surgery, and post-surgery radiotherapy, specially in low-grade sarcoma.

Survival of patients with primary central nervous system diffuse large B-cell lymphoma: impact of gene aberrations and protein overexpression of bcl-2 and C-MYC, and selection of chemotherapy regimens

Objective: To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER). Copy number variation (ICN) and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization (FISH). The relationship between the above indexes and the prognosis was analyzed by univariate, bivariate survival analysis and multiple Cox hazard regression analysis. Results: The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36∶1.00, and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model, 27 cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both bcl-2 gene translocation and ICN were found in 30 patients. Four ICNs of C-MYC gene were found in 28 patients. Elevated protein in cerebrospinal fluid (CSF) was found in 13 patients. LDH increased in 10 cases. Follow-up period was 2-90 months with the average survival time of (23.0±3.7) months and two-year survival rate of 39.0%. Univariate survival analysis showed that overexpression of bcl-2 protein (≥70%) and MYC protein (≥40%), bcl-2 gene abnormality (including copy number increase and translocation), C-MYC gene copy number increased were adverse factors for survival. C-MYC/ bcl-2 gene double hit was seen in 2 cases. Bivariate survival analysis found that of bcl-2/MYC protein double expression and bcl-2 and C-MYC genes double aberration were significantly associated with adverse outcomes. Cox multivariate risk regression analysis found that gender, cerebrospinal fluid protein increasing, and ICN of C-MYC gene were independent poor prognostic factors. DH-MTX based comprehensive chemotherapy was associated with better prognosis. Conclusions: Double hit at genomic level (copy number variations and gene rearrangements) and double protein expression of bcl-2 and C-MYC in PCNS-DLBCL are significantly associated with an adverse outcome. DH-MTX based comprehensive treatment may prolong the patient survival.

Predictors of Asymptomatic Radiation-induced Abdominal Atherosclerosis

AimsTo identify predictors of asymptomatic radiation-induced abdominal atherosclerosis in patients treated with radiotherapy and evaluated by abdominal vascular ultrasonography. Materials and methodsForty-two testicular classic seminoma patients (median age 34 years, range 16–56) undergoing radical inguinal orchiectomy were analysed. Twenty-six patients underwent post-surgery radiotherapy (median total dose 25 Gy, range 25–43), two of them also received chemotherapy (CHT) and 16 patients were treated with surgery alone or by surgery followed by CHT (control group). The presence of stenosis in an abdominal vessel and renal resistive index (RRI), evaluated by echo-colour Doppler (ECD), were considered as indicators of late vascular damage. Chi-square and Mann-Whitney tests were used to compare groups. For the radiotherapy group, near maximum (D2%) and mean dose (Dmean) metrics of critical structures (abdominal arteries and renal hila) were extracted from retrievable dose maps (18 of 26 radiotherapy patients). To evaluate clinical and dosimetric factors associated with vascular damage, univariate and multivariate analyses were carried out. The impact of dose to arteries, evaluated as separate subvolumes, was analysed comparing the stenotic arteries with normal ones by logistic regression. The area under the receiver operator characteristic curve (AUC) was used to evaluate the test accuracy. ResultsIn the radiotherapy group there was a significantly different incidence of stenosis (31% versus 0%, P = 0.016) and a higher median average RRI (0.63 versus 0.60, P = 0.032) compared with the control group. The median time intervals between treatment and ECD were 64 months (range 12–120) and 48 months (range 12–168) in the radiotherapy and control groups (P = 0.399), respectively. A younger age at radiotherapy was the only clinical risk factor for stenosis (P = 0.006). Artery Dmean was significantly associated with stenosis (P = 0.008), with an odds ratio of 1.13 (95% confidence interval 1.01–1.26) and an AUC of 0.85 (95% confidence interval 0.77–0.91). Renal hilum D2% was correlated with RRI (Rs = 0.406, P = 0.02). ConclusionsLate vascular damage represents a potential effect of abdominal radiotherapy, even at a moderate dose. Younger age at irradiation, artery and renal hila dose metrics are associated with increased risk. Ultrasound-based follow-up may allow for non-invasive early detection of asymptomatic radiation-induced damage, helping to prevent severe vascular events.

Omentum: An unusual site for distant metastasis for post-surgery radiotherapy treated squamous cell carcinoma larynx

Squamous cell carcinoma of the larynx is the most common histologic type, accounting for up to 90% of cancers with more predilections to spread locoregionally to the cervical lymph nodes. Distant metastasis, usually to lungs, bone, and liver is seen much less frequently, with an overall incidence of 6.5–7.3%. A case of 55-year-old male with the previous history of surgery and radiotherapy treated squamous cell carcinoma of the larynx, presenting with a chief complaint of pain abdomen is hereby reported for its unusual diagnosis of metastatic deposits of squamous cell carcinoma in the omentum. Though there are reference available for peritoneum as the distant metastatic site for hypopharyngeal carcinoma, reference for laryngeal carcinoma metastasizing to omentum were not found even with an extensive search of literature. Awareness of unusual sites of distant metastasis such as omentum must be kept in mind for treated laryngeal carcinoma patients presenting with non-specific symptoms like pain abdomen. And also, chances of involvement of unusual site of the distant metastasis increases with advanced tumor-node-metastasis stage and nodal status.

Randomized, controlled phase II study of post-surgery radiotherapy combined with recombinant adenoviral human p53 gene therapy in treatment of oral cancer

The aim of this study is to evaluate clinical benefits of recombinant adenoviral human p53 (rAd-p53) gene therapy combined with radiotherapy in prevention of oral cancer recurrence after a radical resection. A total of 51 patients with tongue cancer (TCa) and 56 patients with gingival carcinoma (GCa) satisfying the inclusion criteria were randomly assigned to two groups: the experiment group (EG) and the control group (CG). The EG group received multipoint injections of rAd-p53 into the surgical wound surface at a dose of 1 × 10¹² viral particles after a radical resection. Patients in both EG and CG were given radiotherapy at a total dose of 60 Gy at 3 weeks after surgery. All these patients were followed up for at least 3 years. Two cases (2/27) of TCa and 2 (2/30) in GCa patients had a local recurrence in EG, but 8 (8/24) TCa and 8 (8/26) GCa patients in CG had a local recurrence. Both recurrent rates of TCa (33.3%) and GCa (30.8%) in CG are statistically significantly higher than those of TCa (7.4%) and GCa (6.7%) in EG, respectively. The overall recurrent rate in EG is 7%, which is also statistically significantly lower than that (32%) in CG. The 3-year overall survival (OS) rate and 3-year disease-free survival (DFS) rate of EG is 100% and 93%, respectively. The 3-year OS and DFS rates of CG are 94 and 68%, respectively. Mild or medium fever and flu-like symptoms were more frequently observed in EG and were considered to be associated with application of rAd-p53. Post-tumorectomy wound surface injection of rAd-p53 combining with radiotherapy is a safe and effective regimen for the patients with TGa or GCa.

Molecular biomarkers in the decision of treatment of cervical carcinoma patients

Cervical carcinoma is the third most common cancer in women worldwide. The programs developed for early detection have made that most patients are diagnosed in early stages. Treatment for those patients consists of conservative techniques as surgery or radical radiotherapy; however, the decision between those two therapies is still controversial. Even though in many cases this decision varies according to classical associated risk factors (i.e. tumor stage or age), in the clinical practice, a significant number of patients treated by surgery also receive post-surgery radiotherapy, with the consequent over-treatment and toxic effects. Since response to treatments is conditioned by individual factors, the use of new biological markers as novel predictive factors for both tumor and normal tissues could help clinicians to choose the best treatment schedule for each patient individually. Based on the experience of our institution, we have reviewed the new biological markers in cervical carcinoma patients treated by radiotherapy.

Neuroendocrine tumor of the uterine cervix: a clinicopathologic study of 14 cases

The study explored the clinicopathologic characteristics of the neuroendocrine tumor of uterine cervix (NTUC). The general information and the clinical-pathological characteristics of 14 NTUC cases were reviewed. The median age of the cases was 41 years. Six cases (42.9 %) were FIGO stage Ib1, four cases (28.6 %) were Ib2, one case was IIa2 (7.1 %), one case (7.1 %) was IIb, one case (7.1 %) was IIIb and one case (7.1 %) was IVb. Radical hysterectomy and bilateral salpingo-oophorotomy plus pelvic lymphadenectomy were performed on seven cases: three cases had radical hysterectomy plus pelvic lymphadenectomy; one case had transabdominal hysterectomy; and one case had a residual cervical resection. Four cases had positive pelvic lymph nodes. Two cases (14.3 %) had the tumor infiltrated to the parametrium and five cases (35.7 %) to lymphovascular space. One case had positive margin of vagina. Nine cases (64.3 %) were administered post-surgery radiotherapy and all cases were given adjuvant chemotherapy. The median follow-up time was 10 months. The median disease-free survival was 6 months, and the median total survival time was 18 months. The median estimated survival time was 32.0 months (95 % CI 16.9-47.1 months). NTUC is a very rare malignant tumor of female genital tract. Multi-center cooperation to gather more cases is the best method to explore the biological behavior and for the proper treatment of NTUC.

Scapula alata in early breast cancer patients enrolled in a randomized clinical trial of post-surgery short-course image-guided radiotherapy.

BackgroundScapula alata (SA) is a known complication of breast surgery associated with palsy of the serratus anterior, but it is seldom mentioned. We evaluated the risk factors associated with SA and the relationship of SA with ipsilateral shoulder/arm morbidity in a series of patients enrolled in a trial of post-surgery radiotherapy (RT).MethodsThe trial randomized women with completely resected stage I-II breast cancer to short-course image-guided RT, versus conventional RT. SA, arm volume and shoulder-arm mobility were measured prior to RT and at one to three months post-RT. Shoulder/arm morbidities were computed as a post-RT percentage change relative to pre-RT measurements.ResultsOf 119 evaluable patients, 13 (= 10.9%) had pre-RT SA. Age younger than 50 years old, a body mass index less than 25 kg/m2, and axillary lymph node dissection were significant risk factors, with odds ratios of 4.8 (P = 0.009), 6.1 (P = 0.016), and 6.1 (P = 0.005), respectively. Randomization group was not significant. At one to three months’ post-RT, mean arm volume increased by 4.1% (P = 0.036) and abduction decreased by 8.6% (P = 0.046) among SA patients, but not among non-SA patients. SA resolved in eight, persisted in five, and appeared in one patient.ConclusionThe relationship of SA with lower body mass index suggests that SA might have been underestimated in overweight patients. Despite apparent resolution of SA in most patients, pre-RT SA portended an increased risk of shoulder/arm morbidity. We argue that SA warrants further investigation. Incidentally, the observation of SA occurring after RT in one patient represents the second case of post-RT SA reported in the literature.

Phase II Study of Post-surgery Radiotherapy Combined with Recombinant Adeno-viral Human P53 Gene Therapy in Treatment of Oral Cancer

Objective: To evaluate benefits of Recombinant Adeno-viral Human p53 (rAd-p53) gene therapy combined with radiotherapy in prevention of oral cancer recurrence after a radical resection. Methods: A total of 215 patients with resectable Tongue Cancer (TCa) and 268 patients with resectable Gingival Carcinoma (GCa) satisfying the inclusion criteria and were randomly assigned to two groups: the Experiment Group (EG) and the Control Group (CG). The EG received multi-point injections of rAd-p53 into the wound surface at a dose of 1 × 10 12 Viral Particles (VP) after a radical resection. Both EG and CG were given radiotherapy at a total dose of 60 Gy three weeks after surgery. All these patients will be followed at least for 3 years. Results: Among these 483 cases, 107 patients (57 in EG and 50 in CG) finished 3-years follow-up. Two cases (2/27) of TCa and 2 (2/30) in GCa patients had a local recurrence in EG, but 8 (8/24) TCa and 8 (8/26) GCa patients in CG had a local recurrence. Both recurrent rates of TCa (33.3%) and GCa (30.8%) in CG are statistically significantly higher than that of TCa (7.4%) and GCa (6.7%) in EG, respectively. The overall recurrent rate in EG is 7.0%, which is also statistically significantly lower than that (32%) in CG. Overall 3-years survival (OS) rate of EG is 100% and the progress free survival (PFS) rate is 93.0% and the minimum PFS time is 29 months. The 3-years OS and PFS rates of CG are 94.0% and 68.0%, respectively. Except for self-limited fever, no other adverse reaction was found to be relative to rAd-p53.