In the development of new treatments, it is important to have an understanding of existing treatment options. In diseases such as advanced melanoma where few approved and effective treatment options exist, clinicians may adopt different approaches to manage patients’ dis- ease. Documenting and characterizing current treat- ments and their associated cost is important to define the dominant treatment practice and to quantify the im- pact of existing therapeutic strategies in terms of both clinical benefit for the patient, as well as cost to the healthcare system. Consequently the primary objective of this study is to document treatment patterns and evaluate relevant costs. In particular, to document first- line, second-line and beyond treatments types as well as the frequency with which they are used in patients diag- nosed with unresectable stageIII or stage IV melanoma.
The TNM classification, 7 th edition, is based upon the invasion depth and the number of metastatic lymph nodes . The validity of the stage classification has been confirmed by inspection of a database of more than 100,000 colorectal cancer patients  . In particular, the patients in T1-T2N1 and T1N2a are classified as Stage IIIA in the TNM classification, 7 th edition, and these Stage IIIA patients have a good prognosis  . In other words, these patients with a good prognosis can be distinguished from those StageIII patients who have a poor prognosis by using the TNM classification, 7 th edition. When considering the indications and protocol for postoperative adjuvant chemotherapy, it is essential to distinguish Stage IIIA patients from the remaining StageIII patients. In the present study, the 5-year cancer-specific survival in the patients with Stage IIIA colon cancer was 97.1% and was extremely good. On the other hand, the 5-year cancer-specific survival in the patients with Stage IIIC was 54.4% and was extremely poor. Consequently, StageIII was classified well. Gao et al.  re- ported that the TNM classification, 7 th edition, was sufficiently capable of predicting prognosis in the patients with StageIII colon cancer.
In addition to lymph node involvement, which was confirmed as the most important prognostic factor, the thickness of the primary tumor was identified to independently contribute to prognosis of melanoma patients with loco-regional skin metastases at the time of the initial metastatic spread. No differences in survival were observed between patients with synchronous skin metastasis already present at the time of the excision of the primary tumor, compared to stage I/II patients with skin recurrence or patients with skin metastasis but unknown primary melanoma. Taking the number of involved lymph nodes into account, as already implemented in the AJCC stageIII classification for patients with nodal disease, may allow a more accurate prediction of prognosis for patients with satellite or in-transit metastases.
female patients. Sixty-one (33%) tumors were located in the left colon (defined as descending colon through rectum), 47 (25%) were in the right colon (defined as cecum through trans- verse colon), and 79 (42%) were in the rectum. Of these cancers, 31 were classified as being protruded CRC, whereas 156 were of the ulcer- ated type. With respect to the tumor size, 31 (17%) tumors were < 3 cm, 102 (55%) were 3-5 cm, and 54 (28%) were > 5 cm. With respect to the histological characteristics of the cancers involved, 20 (11%) exhibited highly differentiat- ed features, 109 (58%) were classified as being moderately differentiated, and 58 (31%) were poorly differentiated. Staging of the cancers showed that within our cohort, 124 (66%) patients had stage II CRC and 63 (34%) patients had stageIII cancer. We concluded that this cohort was suitable for determining the relative usefulness of CD44 versus CD44v6 expression as an indicator for disease prognosis.
Although stageIII and IV endometriosis suggest advanced disease, endometrial implants and adhesions are frequently not symmetrically distributed in the pelvis  allowing for the possibility that one adnexa may be relatively free of mechanical factors of infertility. The fact that one adnexa may have less disease may positively influence the pregnancy rate reported as a result of surgical treatment of advanced endometriosis. That is to say, the pregnancy occurs as a result of ovulation/tubal ovum pickup from the side with less adnexal pathology. However, in such cases the resulting pregnancy may be due to the effect of ablation of endometrial implant, as in patients with minimal or mild endometriosis . If such a hypothesis is true, the pregnancy rate should be much less in patients with bilateral adnexal involvement. To examine this hypothesis, we therefore studied the effect of unilateral versus bilateral adnexal involvement on the pregnancy rate after operative laparos- Support: None
it is used for new pharmaceutical products close to launch. The principal evidence for an STA is derived from a submission by the manufacturer/ sponsor of the technology. In addition, a report reviewing the evidence submission is submitted by the evidence review group (ERG); an external organisation independent of the Institute. This paper presents a summary of the ERG report for the STA entitled ‘Rituximab for the treatment of relapsed or refractory stageIII or IV follicular non- Hodgkin’s lymphoma’. 2
Our main or full model analysis incorporates input par- ameter uncertainty and heterogeneity. As mentioned earlier, for input parameters where there is considerable uncertainty, a probability distribution around the best estimate is defined. Our main analysis captures input parameter uncertainty through a ‘looped’ or nested Monte Carlo simulation approach, involving millions of simulations in total. This approach is described in detail by Koerkamp et al. . The effect of this input param- eter uncertainty is then presented as 95 % uncertainty intervals (UIs) for QALYs DW , incremental costs, and ICERs. These main results’ can be presented for all stageIII colon cancer patients combined, but also separately by heterogeneous patient types (e.g. different ethnic groups, young and old) – so called ‘heterogeneity analyses’.
High Estrogen Receptor Alpha Expression Low estrogen level is related to the increase of stageIII-IV uterine prolapse incidence, so that estro- gen deficiency has been identified as a risk factor. It underlay the emerging rationale of hormone replacement therapy for stage I-II uterine prolapse. Even though the therapy had been said to give a protection effect and a correction to stageIII-IV uterine prolapse, the response on women with stageIII-IV uterine prolapse was still uncertain. A study found that serum estradiol concentration and estrogen receptor alpha were lower in pre-meno- pausal women with stageIII-IV uterine prolapse, but no difference in serum estradiol concentration and estrogen receptor alpha in post-menopausal women with the same degree of prolapse. A positive relationship was found between estrogen receptor concentration and the length of menopause, while the estrogen receptor alpha expression and estro- gen hormone level in post-menopausal women relationship was inverse. 25
Introduction: StageIII melanoma, also referred to as regional metastatic melanoma, has five-year survival rates ranging between 40% and 78%. In order to reduce the likelihood of recurrence in this high-risk population, patients undergo resection of primary tumors and all involved nodal basins. Systemic therapy is being pursued in an effort to improve outcome data, but the best strategy has yet to be defined. Interferon alpha-2b remains to date the most promising approach available. Toxicities and intensive intravenous administration, unfortunately, are major concerns. An alternative is the use of interferon in its pegylated subcutaneous form. The aim of this research was to review the evidence for the use of pegylated interferon alpha-2b in StageIII malignant melanoma. Evidence review: ECOG 1684 was the pivotal trial that first demonstrated a statistically significant benefit in relapse-free and overall survival for adjuvant interferon alpha-2b in high-risk melanoma. Other larger studies, such as ECOG 1690, confirmed a relapse-free survival benefit but did not achieve statistical significance for overall survival. The first study of the pegylated form of interferon alpha-2b in StageIII melanoma, EORTC 18991, is reviewed here. This trial showed a statistically significant improvement in relapse-free survival but not overall survival. Encouraging data of potential equivalent efficacy, easier administration, and fewer Grade 3 and 4 adverse reactions compared with high-dose intravenous interferon raises the question of its potential role in StageIII melanoma in the adjuvant setting.
pancreatic remnant is less clear. Because the late devel- opment of a metachronous tumor, particularly one iso- lated to the pancreatic remnant is a relatively rare event, the role of surgery may be more easily justified. Here, a case is presented of a patient who developed a meta- chronous adenocarcinoma of the pancreas 4 years after the initial diagnosis of stageIII pancreatic cancer, treated with upfront curative intent completion pancreatectomy followed by adjuvant chemotherapy and chemoradiation.
The 5-year DFS for the whole group of patients was 53% ± 11% (Table 3). The 5-year DFS for the PORT group was 65% ± 13% compared with 40% ± 9% for the non-PORT group (P = 0.04), as shown in Figure 1. The other studied factors, including stage and pathological type, showed 5-year DFS of 60% ± 15% in stageIII patients compared with 20% ± 6% for stage IV patients, with P = 0.02. There were no significant difference rates of DFS according to histopatho- logical types (transitional cell carcinoma versus squamous
lumen and causing anemia. However, left-sided colon cancers tend to be infiltrating, constricting lesions en- circling the colorectal lumen and causing obstruction. Sex and age disparities have also been reported [4, 5], and different clinicopathologic features of the right colon and left colon have likewise been noted. Meguid et al.  reported a higher proportion of poorly differen- tiated tumors, larger tumors, and stageIII disease in right-sided colon cancers than in left-sided colon can- cers. Similar results have also been presented in other studies [7–10].
Based on the study performed by Sykes A. J., et al. Re- sults of a phase I study to determine the maximum toler- ated dose of capecitabine when given concurrently with radical radiotherapy in the treatment of squamous cell carcinoma of the head and neck . We applied these findings to our study design. In the target group of stageIII/IV head and neck squamous cell carcinoma cases, the response rate using radiotherapy alone is about 70%. It
Retrospective data were collected from January 2009 to December 2014. Eligible patients were pathologically diagnosed as stageIII disease, as classi ﬁ ed according to the eighth edition of Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) gastric cancer staging system. The inclu- sion criteria were as follows: 1) patients aged between 20 and 75 years old, who had undergone radical D2 gastrect- omy; 2) those who had histologically con ﬁ rmed stageIII gastric cancer with no clinical or imaging evidence of distant metastasis (M0); 3) patients with postoperative survival >3 months. The exclusion criteria were as fol- lows: 1) patients who had undergone neoadjuvant treatment(s); 2) adjuvant radiotherapy alone without any combination of chemotherapy; 3) positive surgical resec- tion margins after surgery; 4) inadequate function of important organs (ie, heart, liver and kidney); and 5) coexisting malignancies, or past history of any other cancer(s) and radio/chemotherapy. The study was approved by the ethics committee of Zhongshan Hospital af ﬁ liated to Fudan University and written informed con- sent was obtained for each patient.
More than 400 new lung cancer cases are seen annually at Lehigh Valley Health Network (LVHN), which has supported a thoracic MDC since 2007. Fifteen percent of patients with NSCLC at our institution presented with stageIII disease. Approximately two-thirds of patients with stageIII NSCLC are seen initially in the outpatient setting; the remaining one- third are diagnosed at the time of hospitalization. The patients identified in the outpatient setting are either referred directly to the thoracic MDC or to an individual physician outside of the MDC setting. We compare patients with stageIII NSCLC seen in the thoracic MDC and patients with stageIII NSCLC not seen in the MDC. This analysis will underscore the need for a multi disciplinary approach to the treatment of patients with stageIII lung cancer.
This is to certify that the dissertation entitled “Analysis of pathological response after neoadjuvant chemoradiation in StageIII Breast Cancer” is a bonafide work done by Dr. M.SIVAKUMAR in the Department of Surgical Oncology, College of Oncological sciences, Cancer Institute (WIA), Chennai in partial fulfillment of the University rules and regulations for award of MCh surgical oncology under my guidance and supervision during the academic year 2011 to 2014.
In stage IV NSCLC, the chemotherapy regimen is partly based on the histologic tumour type . However, in stageIII NSCLC, the PROCLAIM phase III trial failed to demonstrate a different survival in patients with stageIII adenocarcinoma when concurrently treated with radiotherapy and cisplatin- etoposide or cisplatin-pemetrexed . This contrasts with the superior overall survival in stage IV adenocarcinoma treated with a platinum-pemetrexed doublet. In advanced disease, molecular characterisation, at least in non-squamous histology, is mandatory and offers the option of targeted therapy [14, 15]. Therefore, accurate determination of the histologic subtype of lung cancer is mandatory in stage IV. It is not yet clear for stageIII [16, 17]. In resected pulmonary carcinomas, histology can provide additional prognostic information beyond TNM staging; until now without therapeutic consequences. For pulmonary adenocarcinoma, comprehensive histologic subtyping, as established by the 2011 IASLC/American Thoracic Society/European Respiratory Society multidisciplinary classification  and included in the 2015 World Health Organisation classification of lung tumours , has been shown to have prognostic relevance independent of tumour stage. The predominant histologic subtype in resected lung adenocarcinoma correlated with overall and disease-free survival in several studies from different countries and even seems to predict benefit from adjuvant chemotherapy in a subset of patients re-evaluated in adjuvant chemotherapy trials . Whether or not the predominant histologic subtype of pulmonary adenocarcinoma evaluated in biopsy specimens carries the same prognostic and predictive significance as shown for tumour resections has yet to be proven. For stereotactic body radiotherapy of the lung there is some hint that the subtype determined from core biopsies is relevant for treatment response and failure patterns . As even small percentages of micropapillary and solid patterns seem to have prognostic impact [22, 23], the detection of any amount of these high-grade patterns in biopsy specimens should have prognostic relevance as well, but sampling error remains a major drawback especially in biopsies with small tumour volumes included . Regarding pulmonary squamous cell carcinoma, no international consensus has been reached on a tumour grading system that adds prognostic information independent of tumour stage, although promising proposals exist [25, 26].
Neuroblastoma is the most common solid extra cranial malignancy in children younger than 15 years. It ac- counts for 8% - 10% of all childhood cancers and 15% of cancer deaths in children . Although this tumor is chemo- and radio-sensitive, it is prone to relapse after initial induction of remission. Stage I and II tumours can be cured with surgery alone, whilst stageIII tumours require preoperative chemotherapy. Sixty percent of neuroblastomas in children are diagnosed in stage IV, of whom many have biological markers of poor prognosis, such as MYCN amplification or 1p deletion . One of the major goals of cancer treatment is to develop thera- pies affecting cancer cells while causing little or no damage to the normal counterparts. In this perspective numerous attempts have been made to bind anti-tumor compounds or radioactive isotopes to molecules specifi- cally taken up by tumour cells. One example of these
this difference in prognosis is due to effects of APC mutations on biology of cancer cells that metastasize to the lymph nodes. Both scenarios are supported by data from literature. With respect to 5-FU treatment, it has been described that CRC patients with APC mutations do not benefit from 5-FU therapy , possibly due to interaction of 5-FU with the APC DNA repair inhibitory domain . Reduced sensitivity to 5-FU was also demonstrated in APC mutant colorectal cancer (CRC) cell lines . Inhibition of DNA replication checkpoint by a Chk1 inhibitor could increase sensitivity of APC-mutant colon cancer cells . With respect to tumor biology, we previously investigated the expression of MGL ligand and demonstrated strong association with DFS in stageIII, but not stage II, colon cancers . High expression of MGL ligand was correlated to BRAF mutations and altered glycosylation, which was thought to subsequently increase immunosuppression by metastasizing cancer cells . We hypothesize that in addition to BRAF mutations also other mutations in the MAPK pathway, possibly in synergy with APC mutations, induce evasion from the immune system.
Three-quarters of cases were menopause at the time of diagnosis. Most patients presented with abnormal vaginal bleeding and had good performance status. Eighty-seven percent of cases (348/400) underwent primary surgery. Most (334/348) of those operations were performed via laparotomic approach. During surgery, 268 and 155 of 334 cases received pelvic and paraaortic nodal evaluation, respectively. Complete removal of disease was achieved in 270 of 348 cases that underwent primary surgery. The most common histologic subtype was endometrioid carcinoma (246/400, 61.5%). Fifty- four percent of cases had high-grade (grade 3) tumor histology. There were 282 (70.5%) and 118 (29.5%) cases that were diagnosed with stageIII and IV disease at first diagnosis, respectively. Demographic, clinical, surgical and pathological characteristics of patients are shown in Table 1.