Postoperative Adjuvant Research Articles

Establishment and effect evaluation of a hierarchical pharmacological monitoring model for immune checkpoint inhibitors.

159 Background: To establish a standardized pharmacy service model for PD-1 monoclonal antibodies through a case study of the practice of full pharmacy service for immune checkpoint inhibitors and to explore the effect of clinical pharmacists' participation in the full pharmacy service for PD-1 monoclonal antibodies. Methods: Patients were graded according to age, pathological stage, Carlson co-morbidity index grading and different treatment stages (preoperative neoadjuvant, postoperative adjuvant and advanced first-line, second-line and third-line or above), whether they had concomitant autoimmune diseases and combination drug use (monotherapy, combination chemotherapy, combination targeted or anti-angiogenic drugs, combination chemotherapy + targeted/anti-angiogenic drugs) to establish PD-1 The effect of this pharmacy service model was evaluated by using the immunotherapy treatment of 132 patients in Shaanxi Provincial People's Hospital who were pharmacologically monitored by clinical pharmacists. Results: 132 patients, 91 males and 41 females, 7 patients aged ≥ 70 years with stage IV tumor and Carlson co-morbidity index ≥ 9 scores were subjected to special grade pharmacological monitoring, 1 patient developed immune myocarditis, 1 patient developed immune pneumonia and reactive capillary hyperplasia, which improved after treatment with methylprednisolone, age < 70 years, stage IV tumor, Carlson Primary pharmacological monitoring was performed in 13 patients with co-morbidity index ≥9 points, of which 10 cases (76.9%) had adverse reactions, 3 cases had pulmonary infections and discontinued, 2 cases had severe thrombosis of grade 3 or higher leading to discontinuation, and the others were hyperthyroidism, hypothyroidism, hypocorticism, etc. Secondary monitoring was performed in the other 112 patients, of which 11 cases (9.8%) had adverse reactions The other cases were immune enteritis, immune encephalitis and immune myocardial injury, and most of the adverse reactions occurred in the 5th cycle after drug administration. Conclusions: By establishing a hierarchical pharmacological monitoring model; patients aged <70 years, stage IV tumors, and Carlson co-morbidity index score ≥9 are at high risk for adverse reactions to immunotherapy, and pretreatment of these patients in advance can ensure the safety of patients' medication, improve medication compliance, and improve patients' quality of life.

Close Surgical Margins in Oral and Oropharyngeal Cancer: Do They Impact Prognosis?

Simple SummaryThe overall survival of patients with close margins was no different than that of others when appropriate postoperative adjuvant and/or salvage treatment were/was prescribed. However, we could not determine the impact of close margins on locoregional recurrence given various biases in our study setting.Introduction. Mucosal margins exhibit a mean shrinkage of 30–40% after resection of oral and oropharyngeal cancers, and an adequate in situ surgical margin frequently results in a pathological close margin. However, the impact on prognosis remains unclear. We investigated the impact of a pathological close margin on disease-free survival (DFS) and overall survival (OS). Methods. We retrospectively reviewed the clinicopathological data of 418 patients diagnosed with squamous cell carcinomas of the oral cavity or oropharynx who underwent initial surgery (with curative intent) at our institute between 2010 and 2016. Results. Of the total population, the pathological marginal status of 290 (69.4%) patients was reported as clear (>5 mm), 61 (14.6%) as close (>1 mm, ≤5 mm), and 67 (16.0%) as positive (≤1 mm). The 5-year DFSs were 79.3%, 65.1%, and 52% in patients in the negative margin (group 1), close margin (group 2), and positive margin (group 3) groups, respectively. The difference between groups 1 and 2 was not significant (p = 0.213) but the difference between groups 2 and 3 was (p = 0.034). The 5-year OSs were 79.4%, 84%, and 52.3% in groups 1, 2, and 3, respectively. The difference between groups 1 and 2 was not significant (p = 0.824) but the difference between groups 2 and 3 was (p = 0.001). In multivariate analysis, older age, advanced T stage, and a positive margin were independently prognostic of the 5-year DFS and OS. Conclusion. In conclusion, the OS of patients with close margins was no different than that of others when appropriate postoperative adjuvant and/or salvage treatment were/was prescribed. However, we could not determine the impact of close margins on locoregional recurrence given various biases in our study setting. A future prospective study is needed.

Clinicopathological features, clinical efficacy on 101 cases of rectal gastrointestinal stromal tumors, and the significance of neoadjuvant therapy

ObjectiveTo investigate the clinicopathological features and clinical efficacy among 101 cases of rectal gastrointestinal stromal tumors (GISTs) and to investigate the significance of imatinib mesylate (IM) neoadjuvant therapy.MethodsThe clinicopathological features, treatment methods, perioperative data, and prognosis of the patients were summarized and analysed in 101 patients with rectal GISTs who received treatment in the Gastrointestinal Surgery of West China Hospital of Sichuan University and the Affiliated Hospital of Guizhou Medical University from August 2002 to November 2020 in China.ResultsA total of 101 patients, including 64 males and 37 females, were aged from 22 to 79 years (55.4 ± 12.2 years). Among the 70 patients who underwent direct surgery, 8 were very low risk cases, 10 were low risk cases, 7 were intermediate risk cases, and 45 were high risk cases. Cox regression analysis showed that postoperative IM adjuvant treatment improved the disease-free survival (DFS) and overall survival (OS) of 52 intermediate and high risk patients. Among the 31 patients who received neoadjuvant therapy, the objective response rate (ORR) was 83.9% (26/31), and the disease control rate (DCR) reached 96.8% (30/31). Subgroup analysis was also conducted based on the tumour diameter. (1) Among the 36 patients with a diameter ≤ 5 cm, two patients received IM neoadjuvant therapy, while 34 patients received direct surgery. Neither univariate nor Cox regression analysis found that neoadjuvant therapy affected DFS and OS. (2) Among the 65 patients with a diameter > 5 cm, 29 received IM neoadjuvant therapy, and 36 received direct surgery. Patients who underwent neoadjuvant therapy had less blood loss (P = 0.022), shorter postoperative hospital stay (P = 0.001), increased anal retention rate (93.1% vs. 72.2%, P = 0.031), and decreased enterostomy rate (10.3% vs. 33.3%, P = 0.037) than those who underwent direct surgery. Cox regression analysis suggested that neoadjuvant therapy and postoperative IM adjuvant therapy improved DFS.ConclusionRectal GISTs are relatively rare and highly malignant tumors. Postoperative oral IM therapy can improve the DFS and OS of intermediate and high risk patients. In patients with rectal GISTs with diameters > 5 cm, IM neoadjuvant therapy can improve anal retention rate, preserve the structure and function of the organs, reduce enterostomy rate, and improve prognosis.

The prognosis of "sandwich" mode of postoperative chemotherapy and radiation in patients with locally advanced cervical cancer.

This study aims to evaluate the survival outcome between different postoperative radiation and chemotherapy modes in locally advanced cervical cancer (LACC). This study is a retrospective cohort study. A total of 150 patients with LACC underwent radical hysterectomy combined with postoperative radiation and /or chemotherapy from October 2009 to October 2019. Of those, 101 patients who received "sandwich" adjuvant chemotherapy and radiation (SCR) were enrolled into group A and 49 patients who received simple radiation were enrolled into group B. The primary outcome was the rates of progression-free survival (PFS) and overall survival (OS). Of 150 patients, 95.3% (143/150) patients complete the study. The rates of deep myometrial invasion (92% and 72.9%, p= 0.007), lymph vascular invasion positive (74.3% and 26.5%, p= 2.59 × 10-8 ), positive surgical margin (11.9% and 0%, p= 0.012), and lymph-node involvement (40.6% vs. 4.1%, p= 4.0× 10-6 ) at baseline were higher in the group A than group B. There was no difference between the follow-up time of group A and group B (45.81 ± 16.83 vs. 45.81 ± 16.84 months, p= 0.665). After the postoperative adjuvant, group A achieved the comparable PFS to group B [p= 0.40; hazard ratio (HR), 1.45; 95% CI, 0.62-3.38]. The cumulative rate of OS in group A was comparable in group B (p= 0.31; HR, 1.53; 95% CI, 0.68-3.45). Postoperative 'sandwich' chemotherapy and radiation could yield a similar survival rate to radiation alone in LACC women with high-risk factors such as deep interstitial infiltration, lymphatic vascular space infiltration, positive resection margin, and lymph-node metastasis.

A new model using artificial intelligence to predict recurrence after surgical resection of stage I-II non-small cell lung cancer.

8537 Background: Five-year survival for stage I-II lung cancer is quite low even after complete surgical resection. Current guidelines recommend adjuvant treatment only for selected patients with stage II or higher disease. A prediction model that identifies patients at high risk of recurrence who may benefit from adjuvant treatment is greatly needed. Many existing prediction models include a small number of genes that were found to be significant in previous studies. We propose using artificial intelligence to analyze a microarray of > 20,000 well-annotated genes to create a model that predicts recurrence after surgical resection of stage I-II lung cancer. Methods: We identified 275 patients who underwent surgical resection for pathologic stage I-II lung adenocarcinoma or squamous cell carcinoma from 2009 to 2019 in our institution’s prospective surgical database. We excluded patients who had follow up time less than 3 years or received adjuvant therapy and had not had a recurrence, as well as patients with missing specimen blocks. Patient characteristics and recurrence information were obtained from chart review. The patients were divided into training (192 patients) and validation (83 patients) cohorts, and the recurrence status for the validation cohort was initially blinded. Gene expression levels were generated using Clariom S human array (ThermoFisher) from 10um sections cut from the formalin-fixed, paraffin-embedded surgical specimen blocks. The artificial intelligence algorithm Support Vector Machine (SVM) was used to create a prediction model for recurrence using the gene expression and recurrence status of the patients in the training cohort. The model was then tested on the validation cohort using Kaplan-Meier analysis and the area under the receiver operator curve (AUROC). Results: The recurrence prediction model separated the validation cohort into 15 (18.1%) patients in the high-risk group and 68 (81.9%) patients in the low-risk group. Kaplan-Meier analysis showed the five-year disease-free survival was significantly higher in the low-risk group compared to the high-risk group (86 vs. 50%, HR = 4.41, p = 0.0025). The AUROC for predicting recurrence was 0.744. Conclusions: Our model uses artificial intelligence to successfully predict recurrence after surgical resection for stage I-II non-small cell lung cancer. With an AUROC of 0.744, our model outperforms previously described models with AUROC up to 0.6. Our model separates patients into high-risk and low-risk groups, which will make management decisions clearer compared to other models that also include an intermediate-risk group. Patients in the low-risk group had 86% five-year disease-free survival; patients in the high-risk group had 50% five-year disease-free survival and may benefit from increased postoperative surveillance or adjuvant therapy.

Postoperative Systemic Acyclovir in Juvenile-Onset Recurrent Respiratory Papillomatosis: The Outcome.

A prospective observational study was conducted consisting of 21 patients of Juvenile-onset recurrent respiratory papillomatosis, attending the Department of Otorhinolaryngology and Head Neck Surgery at our institution, who underwent surgical excision of the papillomas followed by oral acyclovir postoperatively. The study was aimed to observe the effect of systemic acyclovir on postoperative outcomes in children having recurrent respiratory papillomatosis undergoing primary surgical excision. It was observed that the mean interval between surgeries as well as the number of surgical interventions required was significantly lesser when acyclovir was used as a postoperative adjuvant than when surgery was done alone. Hence, the interval between successive surgeries, or in other words, the time interval between relapse of the disease could be prolonged significantly with the use of postoperative systemic acyclovir. Thus, the disease could be controlled for longer periods and repeated surgeries avoided.

Future prospects for breast cancer immunotherapy

Immunotherapy has already become an important component of the standard treatment of patients with advanced cancer. Most treatment methods include monoclonal antibodies (mAbs) that block immune checkpoints, in particular, the programmed cell death 1 (PD-1) receptor and its ligand 1 (PD-L1) or are directed against T-lymphocyte-associated protein 4 (CTLA-4). The future prospects for immuno-oncology will be to determine whether these agents can be more effective if administered in a postoperative adjuvant or in a neoadjuvant regimen prior to surgical treatment. Vaccine therapy has shown promising results, and this therapy is especially attractive due to absence of pronounced toxicity.

Postoperative adjuvant and very early salvage radiotherapy after prostatectomy in high-risk prostate cancer patients can improve specific and overall survival

Adjuvant radiotherapy (ART) for biochemical relapse (BR) after radical prostatectomy (RP) showed increased disease-free survival (DFS) in three previous randomized trials. Retrospective phase II trials evaluated if early salvage RT (ESRT) is equivalent to ART. Our study aims to compare ART and ESRT to salvage RT. We compared RP plus ART and ESRT versus SRT. Indication for RT was made by PSA determination after RP: ART when PSA ≤ 0.2ng/ml, ESRT when PSA ≤ 0.3 after PSA rise from 0.0 to SRT PSA ≥ 0.3. The cause of death of each patients was analyzed, DFS, cause-specific survival (CSS) overall survival (OS) and metastasis-free survival (MFS) in relation to RT intention. Between 1993 and 2008, 204 patients with a median age of 65years (44-75) were treated. The median follow-up was 160months (28.1-273.3). At diagnosis, 89.7% had localized clinical stages and 90.2% had Gleason (G) ≤ 7. The median PSA was 10 (range 4-101). The postoperative G was ≥ 7 in 66.2%; 56.4% had ≥ 2 positive margins; 29.4% received ART, 20% ESRT and 59.3% SRT. The DFS for ART, ESRT and SRT was 74, 56 and 39% with significant differences between the three groups (p < 0.001). ART + ESRT were combined versus SRT; for the DFS, the significant differences (p < 0.001) remained 67% versus 39%. Positive margins, pT3 and pre-RT PSA were significant factors on multivariate analysis. The CSS in the ART + ESRT group was 92 vs. 78% in the SRT group (p < 0.05). OS was 69% in ART + ESRT vs. 57% in SRT (p < 0.05). MFS was 82.7% in ART + ESRT vs. 67.4% in SRT. In this study the ART + ESRT presented benefits versus SRT in DFS, CSS, OS and MFS.

Carcinoma de Lengua Móvil.

Introducción: El Carcinoma de lengua móvil es uno de los tumores malignos más frecuentes de la cavidad bucal. Generalmente, los pacientes son diagnosticados después de los 40 años de edad. La detección temprana de estas lesiones, evita su desarrollo hacia fases avanzadas de la enfermedad, que oscurecen su pronóstico, por medio de una atención rápida y adecuada, biopsia oportuna, y tratamiento precoz, evitando que los pacientes sean mutilados, sufran o mueran por esta causa. El objetivo del presente estudio es reportar un grupo de pacientes con esta neoplasia, su tratamiento y supervivencia. Métodos: En el presente estudio descriptivo, longitudinal y retrospectivo fueron evaluados los pacientes con diagnóstico de carcinoma de lengua móvil, tratados en el Instituto Nacional de Oncología de la Habana, entre los años 2007 y 2011. Se reporta edad, tabaquismo, alcoholismo, estadiaje, tipo de tratamiento y supervivencia. Resultados: Se registraron 68 casos, se observó un predominio del grupo de edad entre los años 55-69, con el 41.18% de los pacientes, siendo el sexo predominante el masculino, con un 79.41% del total. En la clasificación TNM, se observó que predominó de los tumores estadiados como T3 con el 35.29 %, seguidos de los T2 con el 30.88 %, la invasión ganglionar estuvo más representada por la categoría N0 con el 58.82% de los casos. El 64.71% de los pacientes estaban vivos a los 60 meses. Conclusión: El carcinoma de lengua móvil fue más frecuente en las edades entre 55-69 años y en el sexo masculino, más del 50% de los pacientes practicaban hábitos tóxicos, hubo un predominio de etapas avanzadas, la cirugía con adyuvancia postoperatoria fue la terapéutica más común.

Neoadjuvant pembrolizumab in surgically resectable, locally advanced HPV negative head and neck squamous cell carcinoma (HNSCC).

6012 Background: Pembrolizumab has efficacy in metastatic HNSCC. We hypothesized that treatment intensification in surgically resectable HPV-negative, Stage III/IV HNSCC with neoadjuvant plus post-operative adjuvant (POA) pembrolizumab would be safe and reduce 1-year locoregional recurrence/distant metastases (LRR/DM) from 35% (historical: Cooper and Bernier NEJM 2004) to 15%. Methods: Phase II trial where all eligible patients received 1 dose of pembrolizumab (200 mg) prior to surgery and only those with high-risk pathologic features (HRPF: extracapsular extension/positive margin) were given POA cisplatin and radiation followed by pembrolizumab. PD-L1 staining was assessed by immunohistochemistry (9A11 antibody). Results: The study continues to enroll. Characteristics of 21 enrolled patients (pts) were median age 59 (32-87) yrs, tobacco use 81% (17 pts), clinical T2 (n = 2), T3 (n = 1), T4 (n = 18), and cN0/1 (n = 8), cN2 (n = 13). Preliminary analyses revealed five important findings: 1) No serious study drug-related AEs or unexpected surgical delays/complications, 2) No LRR/DM events in the first 10 patients with &gt; 1-year follow-up after surgery 3) HRPF rate of 38% (95% CI: 18%-62%) (expected: 80%), 4) 43% of pts (95% CI: 22%-66%) with pathologic treatment response to neoadjuvant pembrolizumab (definition: tumor necrosis and/or giant cell/histiocytic reaction to keratinous debris in &gt; 10% of tumor area), and 5) 48% of pts (95% CI:26%-70%) with clinical-to-pathologic downstaging. Pathologic treatment effect (TE) in ≥ 70% of the resected tumor or lymph node tissue area occurred in 6/21 pts (29%). Baseline tumor biopsies were PD-L1 positive ( &gt; 1% of tumor cells) in 11/19 (58%) evaluable samples and in 7/8 (88%) evaluable pathologic responders. A significant correlation existed between baseline PD-L1 expression on tumor cells and pathologic treatment effect in the tumor (correlation coefficient: 0.72 and p = 0.0005). Conclusions: Neoadjuvant and adjuvant pembrolizumab was safe and well tolerated. We observed several lines of evidence supporting an anti-tumor effect in these pts with a single dose of pre-operative pembrolizumab. Further evaluation of this strategy is warranted. Clinical trial information: NCT02296684.

Orthovoltage X-rays for Postoperative Treatment of Resected Basal Cell Carcinoma in the Head and Neck Area.

Surgery is the golden standard for treating basal cell carcinomas. In case of positive tumor margins or recurrent disease, postoperative adjuvant or salvaging therapy is suggested to achieve good local control. To retrospectively report on local control and toxicity of postoperative radiotherapy by means of orthovoltage X-rays for residual or recurrent basal cell carcinoma after surgery in the head and neck area. Sixty-six surgically resected residual or recurrent basal cell carcinomas of the head and neck region were irradiated postoperatively by means of orthovoltage X-rays at the Netherlands Cancer Institute between January 2000 and February 2015. After a median follow-up duration of 30.5 months, only 5 recurrences were reported. The 5-year local control rates at 1, 3, and 5 years were 100%, 87%, and 87%, respectively. The 5-year local control rate was 92% for immediate postoperative radiotherapy of incompletely resected basal cell carcinomas, 90% for recurrences after 1 previously performed excision, and 71% for multiple recurrences, namely, a history of more than 1 excision ( P = .437). Acute toxicity healed spontaneously within 3 months. Late toxicities were mild. Radiotherapy by means of orthovoltage X-ray is an excellent alternative for re-excision in case of incompletely resected or recurrent basal cell carcinomas that are at risk of serious functional and cosmetic impairments after re-excision, with a 5-year local control rate of 87% and a low toxicity profile.

Changes of diagnosis and treatment for gastrointestinal stromal tumors during a 18-year period in four medical centers of China

To elucidate the historic and current diagnosis and treatment status of gastrointestinal stromal tumor (GIST) in the Chinese population based on four high volume databases. Clinicopathological data of GIST patients with follow-up information between January 1998 and December 2015 from Sun Yat-sen University Cancer Center, Union Hospital of Huazhong University of Science and Technology, Southern Medical University Nanfang Hospital and Guangdong General Hospital were retrospectively analyzed. Kaplan-Meire method was used to draw survival curve. The accumulative survival rate was calculated by life table method. Comparison of survival rate among groups was examined by Log-rank test. A total of 2 610 cases were enrolled into the study, including 667(25.6%) cases from Sun Yat-sen University Cancer Center, 754(28.9%) cases from Union Hospital of Huazhong University of Science and Technology, 692(26.5%) cases from Southern Medical University Nanfang Hospital and 497 (19.0%) cases from Guangdong General Hospital. There were 1 394 male and 1 216 female cases with the ratio of 1.15 to 1.00. The age of patients was from 18 to 95 (median 58.0) years old. Three-year was used as a time stage, then 18 years were divided into 6 stages. New GIST patients increased gradually year by year. There were 13(0.5%) cases during 1998 to 2000, 68(2.6%) cases during 2001 to 2003, 256(9.8%) cases during 2004 to 2006, 517 (19.8%) cases during 2007 to 2009, 814(31.2%) cases during 2010 to 2012, and 942 (36.1%) cases during 2013 to 2015. Primary GIST sites were esophagus in 50(1.9%) cases, stomach in 1 686(64.6%) cases, duodenum in 206 (7.9%) cases, jejunum and ileum in 446 (17.1%) cases, colon and rectum in 133 (5.1%) cases, and non-gastrointestinal tract in 89 (3.4%) cases. GIST lesions of 2 404(92.1%) cases located in the primary sites and relapse/metastasis occurred in 206 cases when consulting. Among 206 relapse/metastasis cases, liver metastasis was found in 126 (61.2%) cases, abdominal cavity/pelvic cavity metastasis in 64 (31.1%) cases, liver plus abdominal cavity/pelvic cavity metastasis in 12 (5.8%) cases, and other site metastasis in 4 (1.9%) cases. Among all the patients, 352 received gene detection, including 1 (0.4%) during 2004 to 2006, 7 (1.4%) during 2007 to 2009, 150 (18.4%) during 2010 to 2012, and 194 (20.6%) during 2013 to 2015. Most of the primary oncogenic mutational site occurred in c-Kit, including 30 (8.5%) cases in exon 9, 242 (68.8%) cases in exon 11, 4 (1.1%) cases in exon 13, 2 (0.6%) cases in exon 17, while 3 (0.9%) cases in PDGFRA exon 12 and 20 (5.7%) cases in PDGFRA 18, besides, no mutations of KIT and PDGFRA were detected in 51 (14.5%) cases. A total of 2 202 cases underwent operation, including 2 038 (92.6%) of radical resection and 164 (7.4%) of palliative resection. Among 2 038 patients undergoing radical resection, 450 (22.1%) cases were very low risk, 593 (29.1%) cases were low risk, 283 (13.9%) cases were moderate risk and 712 (34.9%) cases were high risk according to NIH risk classification. Of 995 patients with moderate and high risk, 550(55.3%) cases received postoperative imatinib adjuvant therapy, whose ratio in above 6 time stages was as follows: 0, 42.8%(12/28), 19.8%(20/101), 9.8% (21/215), 65.7% (176/268) and 85.6% (321/375). Of 206 relapse/metastasis patients, 200 (97.1%) cases received imatinib as the first-line therapy, and 22 (10.7%) received sunitinib as the second-line therapy. A total of 1 743 patients had complete follow-up data and median follow-up time was 35.9 (0.1 to 173.8) months. The 5-year overall survival rates in very low, low, moderate and high risk patients were 100%, 97%, 95% and 78% respectively. This retrospective study provides the largest data of GIST and indicates the historic changes of clinicopathological characteristics, diagnosis and treatment of GIST for further domestic GIST research.

Role of preoperative versus postoperative itraconazole in allergic fungal rhinosinusitis.

Antifungals used as adjuvant to surgery in AFRS (Allergic Fungal Rhinosinusitis) have shown varying success in delaying recurrences. Itraconazole has been used both as preoperative and postoperative adjuvant. This study investigates the role of itraconazole in AFRS and compares its role between preoperative and postoperative administration of the drug. Patients were randomly divided into groups as: Group 1 (n = 25), received 4 weeks itraconazole in the preoperative period and operated subsequently, Group 2 (n = 25), received 4 weeks itraconazole in the postoperative period, Group 3 (n = 50), matched patients of AFRS, who didn't receive itraconazole. All the groups received oral steroids in tapering doses staring from 1mg/kg for 6 weeks in the postoperative period. Symptomatic (SNOT 20), radiologic (Lund Mackay, LM) scores and endoscopic (Kupferberg's NE Grades) were noted. Primary postoperative follow-up was for 24 weeks with routine CT scans and nasal endoscopies, followed by which all the patients were followed with nasal endoscopies only with CT scans when required. Both preoperative and postoperative itraconazole showed significant improvement in the SNOT, LM, and Kupferberg's grades in the follow-up period. Preoperative itraconazole therapy showed significantly better results compared to postoperative itraconazole therapy though the recurrence rates were similar in both groups. Itraconazole is a better preoperative adjunct in AFRS than postoperative.

Do we need 18F-FDG PET/CT scan in staging and management of testicular tumors?

ObjectiveThe aim of this study was to assess the role of positron emission tomography/computed tomography (PET/CT) scan in preoperative staging of testicular tumors and therefore determining the line of appropriate management. Patients and methodsDuring two year duration we prospectively evaluated 34 patients with testicular tumors diagnosed by histopathology after biopsy or orchidectomy. All patients underwent PET/CT examinations following a preset protocol that included low dose non contrast study, whole body scanning post 18F-FDG injection and post IV contrast CT scan. The images obtained were reconstructed using dedicated software and workstations. Results of PET/CT examinations were compared with histopathology and serum markers. ResultsOut of 34 cases all masses were malignant (germ cell tumors). 20 masses (58.8%) were diagnosed by histopathology as seminoma subtype while 14 masses (41.2%) were diagnosed as non seminomatous germ cell tumors (NSGCT) subtype.There were 16 true positives, 14 true negatives, 2 false positive, and 2 false negative cases. Sensitivity, specificity, positive predictive value and negative predictive values were 88.9%, 87.5%, 88.9% and 87.5% respectively. ConclusionPositron emission tomography/computed tomography (PET/CT) has a major role in preoperative staging of testicular tumors and defines the need of post operative adjuvant therapy.

An update in the management of spinal metastases.

The best clinical treatment for spinal metastases requires an integrated approach with input from an interdisciplinary cancer team. The principle goals of treatment are maintenance or improvement in neurologic function and ambulation, spinal stability, durable tumor control, and pain relief. The past decade has witnessed an explosion of new technologies that have impacted our ability to reach these goals, such as separation surgery and minimally invasive spinal procedures. The biggest advance, however, has been the evolution of stereotactic radiosurgery that has demonstrated durable tumor control both when delivered as definitive therapy and as a postoperative adjuvant even for tumors considered markedly resistant to conventional external beam radiation. In this paper, we perform an update on the management of spinal metastases demonstrating the integration of these new technologies into a decision framework NOMS that assesses four basic aspects of a patient's spine disease: Neurologic, Oncologic, Mechanical Instability and Systemic disease.

Superficial ocular malignancies treated with strontium-90 brachytherapy: long term outcomes.

PurposeThe incidence of conjunctival malignancies is less than 1%. Though surgical excision remains the mainstay of treatment, the incidence of positive surgical margins and local recurrence rates are high, which is approximately up to 33% in negative margins and 56% in positive margins. Radiotherapy reduces the risk of recurrence in these cases. Brachytherapy using β emitters such as strontium-90 (90Sr) is an ideal treatment technique for these tumors with the advantage of treating only a few millimeters of tissue while sparing the underlying normal eye. We report the long term outcomes in the form of local control and late sequelae of patients with conjunctival malignancies treated with 90Sr applicator brachytherapy.Material and methodsDuring 1999-2013, 13 patients with conjunctival tumors, treated using 90Sr brachytherapy were analyzed. Brachytherapy was either in a post-operative adjuvant or in a recurrent setting. Local control (LC), disease free survival (DFS), overall survival (OS), and late sequelae were evaluated.ResultsThe median age at presentation was 47 years (range: 11-71 years). Thirteen patients with 15 tumors were treated. The commonest histology was squamous cell carcinoma. The median dose was 44 Gy over 11 fractions. The median follow up of all the patients was 51 months (range: 3-139 months). The median follow up of patients with carcinoma only was 64 months with a LC and DFS of 90.9% at 5 years. None of the patients developed ≥ grade II Radiation Therapy Oncology Group (RTOG) acute toxicities. One patient developed a focal scar and another developed corneal opacification at the limbus. Vision was not impaired in any of the patients.ConclusionsStrontium-90 brachytherapy used in early invasive conjunctival malignancies as an adjunct to surgery in primary and recurrent settings, results in optimal disease control and ocular functional outcomes.

Anticancer activity of tuftsin-derived T peptide in postoperative residual tumors

Immune adjuvants have been used in cancer biotherapies to stimulate immune response to tumor cells. Despite their potential as anticancer reagents, there are several impediments to their use in clinical applications. In this study, we aim to modify the existing tuftsin structure and evaluate its antitumor activity in preclinical models. We synthesized a novel tuftsin derivative, namely, the T peptide (TP), by linking four tuftsin peptides, which showed enhanced stability in vivo. We then evaluated its anticancer activity in a postoperative residual tumor model in mice, where we surgically removed most of the primary tumor from the host, a procedure mimicking clinically postoperative patients. Despite the limited effect in intact solid tumors, TP strongly inhibited relapsed growth of residual tumors in postsurgical mice. Surgical resection of tumors accelerated residual tumor growth, but TP slowed down this process significantly. Interestingly, TP showed similar effects in human xenograft residual models. As an immunomodulator, TP could synergize the functions of macrophages, thus inhibiting the growth of cocultured tumor cells in vitro. Furthermore, TP could shift the macrophages to the tumor-suppressive M1 type and mobilize them to produce elevated cytotoxic TNF-α and NO. As a result, TP effectively prolonged the survival time of tumor-resected mice. Using the postoperative residual tumor models, we provide a body of evidence showing the antitumor activity of TP, which causes no obvious toxicity. Our study highlights the potential of TP as a postoperative adjuvant in cancer therapies.

Severe gastrointestinal bleeding in patients with locally advanced head and neck squamous cell carcinoma treated by concurrent radiotherapy and Cetuximab.

Concurrent administration of Cetuximab with radiotherapy (Cetuximab-radiation) has been accepted as an alternative option for locally advanced head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to retrospectively compare complications of Cetuximab-radiation with those of concurrent chemoradiation (cCRT) with a special concern on gastrointestinal (GI) hemorrhage associated with Cetuximab-radiation. Indication of Cetuximab-radiation/cCRT for locally advanced HNSCC was primary, postoperative adjuvant, or salvage after recurrence. Our first choice for patients with advanced HNSCC was cCRT; however, if patients did not have enough organ function but with a favorable performance status, Cetuximab-radiation was applied. From April 2013 to March 2014, 30 patients were identified who were treated with Cetuximab-radiation or cCRT and each cohort consisted of 15 patients. Patients in Cetuximab-radiation cohort suffered from a statistically higher rate of G3/4 dermatitis compared with cCRT cohort (80 vs. 13.3%, respectively, p < 0.001). More patients required unexpected hospitalization due to deterioration of their general condition and total parenteral nutrition in Cetuximab-radiation cohort (p = 0.011 and p = 0.025, respectively). While none experienced GI bleeding in cCRT cohort, four patients experienced GI bleeding including two grade 4 bleeding in Cetuximab-radiation cohort (p = 0.05). It is probable that there exists a group of patients who are susceptible for Cetuximab-radiation not only in terms of well-known dermatitis and mucositis but also of gastrointestinal complications.

Stereotactic radiosurgery for primary malignant spinal tumors

Objectives:We adopted stereotactic radiosurgery (SRS) to treat primary malignant spinal tumors. The objective of this study was to evaluate local control rate and to identify prognostic factors after SRS for primary malignant spinal tumors.Methods:Medical records and radiological data for 29 patients with primary malignant spinal tumors were retrospectively analyzed. The histological diagnoses were chordoma (11 cases), chondrosarcoma (5 cases), osteosarcoma (3 cases), synovial sarcoma (3 cases), plasmacytoma (2 cases), Ewing sarcoma (2 cases), malignant peripheral nerve sheath tumor (2 cases), and malignant fibrous histiocytoma (1 case). Patient age ranged from 11 to 68 years (median, 46 years). Surgical resection and percutaneous biopsy were chosen as initial treatments in 25 and 4 cases, respectively. Stereotactic radiosurgery was used as primary treatment method in 14 cases and as a salvage treatment for progressed lesions in 15 cases. Distant metastasis was noted in two sarcoma patients. Eleven patients had undergone previous conventional external beam radiation therapy (cEBRT) before SRS. Overall survival, local progression-free survival, and the prognostic factors affecting local recurrence were investigated.Results:Tumor volume ranged from 2·0 to 235 cc (median, 14 cc). Delivered radiation doses were from 12 to 50 Gy with two to six sessions. The mean radiation dose converted into a biological effective dose (BED) was 60 Gy (range, 43–105 Gy). The mean follow-up period was 50 months (range, 8–126 months). The mean overall survival was 84 months for chordoma patients and 104 months for sarcoma patients. No factors that affected overall survival were found. The mean local progression-free survival was 56 months for chordoma patients and 73 months for sarcoma patients. The recurrent mode of presentation was predictive of local progression of spinal sarcomas (P = 0·009). However, in chordoma patients, no factors were found to correlate with local recurrence.Conclusion:These preliminary results suggest that SRS could provide good local control when applied as postoperative adjuvant or salvage treatment after cEBRT for primary malignant spinal tumors.

Local recurrence map to guide target volume delineation after radical prostatectomy

PurposeTo describe the various anatomic locations of recurrent disease, in a cohort of men with radiographically visualized, biopsy-proven recurrent prostate cancer after radical prostatectomy (RP), in order to help guide contouring of the prostatic fossa clinical target volume (PF-CTV) when no gross recurrence is visible or when magnetic resonance imaging (MRI) is not used. Methods and materialsTen representative patients with MRI-detected, biopsy-proven local recurrences of prostate adenocarcinoma after RP were selected. Areas of recurrence were delineated on individual MRI images, and then mapped onto axial and sagittal “template” MRI images to compositely demonstrate the documented areas of recurrence. Coverage of these anatomic areas of recurrence was then evaluated by applying Radiation Therapy Oncology Group (RTOG)-consensus PF-CTV contours to a postoperative computed tomographic template. ResultsThe median age at the time of RP was 61 years (range, 50-73). In the superoinferior direction, recurrences ranged from the superior retrovesical region, to the inferior retrovesical region, to the posterior anastomosis, and as inferiorly as the posterior urogenital diaphragm. In the anteroposterior direction, the areas of recurrence ranged from involving the posterior bladder wall anteriorly to invading the rectum posteriorly. Recurrences were found at the center, right, and left of the prostate and seminal vesicle fossa. When target volumes were delineated using RTOG-defined consensus PF-CTV contours, coverage was marginal on recurrences in the posterolateral aspects of the CTV near the rectum and mesorectal fascia and lacking on recurrences occurring inferiorly at the posterior urogenital diaphragm. ConclusionsOur findings describe the variation in location of prostate cancer recurrences and can be used to improve target definition in conformal radiation therapy in the postoperative adjuvant or salvage setting. RTOG-consensus contours for the PF-CTV should be applied carefully, with potential modifications in the posterolateral and inferior aspects.