Neoplasm Recurrence, Local
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Neoplasm Recurrence, Local
Description
The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site.Read more
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Pubmed
Clear cell carcinoma of the cervix: a multi-institutional review in the post-DES era.
Journal: Gynecologic oncology
June/18/2008
Description

OBJECTIVE

To conduct an outcome analysis of patients with cervical clear cell carcinoma (CCCC) in the post-DES era.

METHODS

A retrospective review was conducted at 3 major gynecologic cancer centers of all primary CCCC between 1982 and 2004.

RESULTS

CCCC was confirmed in 34 patients. Median age was 53 years. DES exposure was confirmed in 2 (6%) patients. A history of smoking was elicited in 22%, and of abnormal Pap smear 18% patients. Primary surgical resection was performed in all stage I or IIA patients (n=26); they displayed superior 3-year overall survival (OS) compared to advanced stage (n=8) patients (91% vs. 22%, p<0.001). Pelvic lymph node involvement was noted in 25%; all patients with positive para-aortic nodes (20% of patients sampled) had positive pelvic nodes. All node positive patients were treated with adjuvant radiation, but nevertheless displayed reduced progression free (31% vs 92%, p<0.001) and overall survival (80% vs. 100%, p=0.02). Adjuvant radiotherapy did not appear to impact OS in patients with negative lymph nodes.

CONCLUSIONS

This series provides insight into the management of early stage CCCC in the post-DES era. Although these patients may be at slightly higher risk of nodal spread, clear cell histology by itself does not appear to portend a worse prognosis than squamous cell carcinoma of the cervix in the absence of traditional risk factors. Our data suggest that patients with low risk early stage CCCC may be managed with radical surgery alone, without the need for adjuvant chemotherapy or radiation.

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Pubmed
Neoadjuvant interleukin-12 immunogene therapy protects against cancer recurrence after liver resection in an animal model.
Journal: Annals of surgery
June/6/2000
Description

OBJECTIVE

To evaluate the neoadjuvant use of a herpes simplex viral (HSV) amplicon vector expressing the murine interleukin-12 (IL-12) gene.

BACKGROUND

Surgery is the most effective therapy for hepatic malignancy. Recurrences, which are common, most often occur in the remnant liver and are due partly to growth of residual microscopic disease in the setting of postoperative host cellular immune dysfunction. The authors hypothesized that engineering tumors to secrete IL-12 in vivo would elicit an immune response directed at residual tumor and would reduce the incidence of recurrence after resection.

METHODS

Solitary hepatomas were established in Buffalo rat livers and directly injected with 106 particles of HSV carrying the gene for IL-12, lacZ (beta-galactosidase) or with saline. One week after injection, the animals were challenged with an intraportal injection of 106 tumor cells, with subsequent resection of the hepatic lobe containing the previously established macroscopic tumor nodule, recreating the clinical scenario of residual microscopic cancer.

RESULTS

Hepatoma cells transfected with HSV-IL-12 produced high levels of IL-12 in vitro and in vivo. A significant local immune response developed, as evidenced by a progressive increase in the number of CD4(+) and CD8(+) lymphocytes in the tumor. Treatment of established hepatomas with HSV-IL-12 protected against growth of microscopic residual cancer after hepatic resection. Sixty-four percent of the animals treated with HSV-IL-12 had zero or one tumors compared with 30% of HSVlac-treated and 24% of saline-treated animals.

CONCLUSIONS

This neoadjuvant immune strategy may prove useful in reducing the incidence of cancer recurrence after hepatic resection.

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Pubmed
Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT.
Journal: Journal of hematology & oncology
October/16/2016
Description

BACKGROUND

Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown.

METHODS

We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT for patients with acute myeloid (AML) or lymphoid leukemia (ALL) after RIC (n = 271) and MAC (n = 425). Regimens were classified as MAC or RIC based on published criteria.

RESULTS

A combination of post-transplant cyclophosphamide (PT-Cy) with one calcineurin inhibitor and mycophenolate mofetil (PT-Cy-based regimen) for graft-versus-host disease (GVHD) prophylaxis was used in 66 (25%) patients in RIC and 125 (32%) in MAC groups. Patients of RIC group were older and had been transplanted more recently and more frequently for AML with active disease at transplant. Percentage of engraftment (90 vs. 92%; p = 0.58) and day 100 grade II to IV acute GVHD (24 vs. 29%, p = 0.23) were not different between RIC and MAC groups. Multivariable analyses, run separately in AML and ALL, showed a trend toward higher relapse incidence with RIC in comparison to MAC in AML (hazard ratio (HR) 1.34, p = 0.09), and no difference in both AML and ALL in terms of non-relapse mortality (NRM) chronic GVHD and leukemia-free survival. There was no impact of conditioning regimen intensity in overall survival (OS) in AML (HR = 0.97, p = 0.79) but a trend for worse OS with RIC in ALL (HR = 1.44, p = 0.10). The main factor impacting outcomes was disease status at transplantation (HR ≥ 1.4, p ≤ 0.01). GVHD prophylaxis with PT-Cy-based regimen was independently associated with reduced NRM (HR 0.63, p = 0.02) without impact on relapse incidence (HR 0.99, p = 0.94).

CONCLUSIONS

These data suggest that T-replete haplo-SCT with both RIC and MAC, in particular associated with PT-Cy, are valid options in first line treatment of high risk AML or ALL.

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Pubmed
Clinicopathologic study associated with long-term survival in Japanese patients with node-negative breast cancer.
Journal: British journal of cancer
February/3/2000
Description

This study was undertaken to determine the absolute and relative value of blood vessel invasion (BVI) using both factor VIII-related antigen and elastica van Gieson staining, proliferating cell nuclear antigen (PCNA), p53, c-erbB-2, and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including PCNA, p53, c-erbB-2 using permanent-section immunohistochemistry, clinical tumour size (T), histological grade (HG), mitotic index (MI), tumour necrosis (TN), lymphatic vessel invasion (LVI) and BVI, followed for a median of 10 years (range 1-20). Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that BVI, PCNA, T, HG, MI, p53, c-erbB-2 and LVI were significantly predictive of 20-year RFS or OS. Multivariate analysis showed that BVI (P = 0.0159, P = 0.0368), proliferating cell nuclear antigen (PCNA) (P = 0.0165, P = 0.0001), and T (P = 0.0190, P = 0.0399) were significantly independent prognostic factors for RFS or OS respectively. BVI, PCNA and T were independent prognostic indicators for RFS or OS in Japanese patients with node-negative breast cancer and are useful in selecting high-risk patients who may be eligible to receive strong adjuvant therapies.

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Pubmed
Androgen receptor phosphorylation at serine 308 and serine 791 predicts enhanced survival in castrate resistant prostate cancer patients.
Journal: International journal of molecular sciences
April/6/2014
Description

We previously reported that AR phosphorylation at serine 213 was associated with poor outcome and may contribute to prostate cancer development and progression. This study investigates if specific AR phosphorylation sites have differing roles in the progression of hormone naïve prostate cancer (HNPC) to castrate resistant disease (CRPC). A panel of phosphospecific antibodies were employed to study AR phosphorylation in 84 matched HNPC and CRPC tumours. Immunohistochemistry measured Androgen receptor expression phosphorylated at serine residues 94 (pAR94), 308 (pAR308), 650(pAR650) and 791 (pAR791). No correlations with clinical parameters were observed for pAR94 or pAR650 in HNPC or CRPC tumours. In contrast to our previous observation with serine 213, high pAR308 is significantly associated with a longer time to disease specific death (p = 0.011) and high pAR791 expression significantly associated with a longer time to disease recurrence (p = 0.018) in HNPC tumours and longer time to death from disease recurrence (p = 0.040) in CRPC tumours. This observation in CRPC tumours was attenuated in high apoptotic tumours (p = 0.022) and low proliferating tumours (p = 0.004). These results demonstrate that understanding the differing roles of AR phosphorylation is necessary before this can be exploited as a target for castrate resistant prostate cancer.

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Pubmed
Clinical significance and treatment of biochemical recurrence after definitive therapy for localized prostate cancer.
Journal: Surgical oncology
November/4/2009
Description

OBJECTIVE

Radical prostatectomy and external beam radiation therapy are the established and definitive interventions for clinically localized prostate cancer. These treatment modalities are yet subject to failure observed first by biochemical recurrence, defined by increases in the serum PSA level. We investigated the significance of biochemical recurrence after definitive therapy and the available salvage therapy options for cancer recurrence.

METHODS

A literature search was performed in PubMed, and applicable studies addressing biochemical recurrence and salvage options after radical prostatectomy or external beam radiation therapy were reviewed.

RESULTS

After radical prostatectomy, a detectable serum PSA level indicates biochemical recurrence. Whether to administer salvage therapy locally or systemically depends largely on prognostic factors including PSA doubling time, Gleason's score, pathologic stage, and the time interval between radical prostatectomy and biochemical recurrence. Early initiation of salvage therapy has been shown to significantly impact on cancer outcomes. After external beam radiation therapy, no single PSA level can define biochemical recurrence. Instead, it has been defined by increases in the PSA level above the nadir. Following radiation therapy, PSA doubling time and Gleason score play important roles in determining the need for local versus systemic salvage therapy.

CONCLUSIONS

After the diagnosis of biochemical recurrence, it is critical to perform a timely clinical assessment using the prognostic factors mentioned above. Prompt initiation of salvage therapy may prevent subsequent clinical progression and prostate cancer-specific mortality.

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Pubmed
Targeted intraoperative radiotherapy for breast cancer in patients in whom external beam radiation is not possible.
Journal: International journal of radiation oncology, biology, physics
June/20/2011
Description

OBJECTIVE

External beam radiation therapy (EBRT) following wide local excision of the primary tumor is the standard treatment in early breast cancer. In some circumstances this procedure is not possible or is contraindicated or difficult. The purpose of this study was to determine the safety and efficacy of targeted intraoperative radiotherapy (TARGIT) when EBRT is not feasible.

METHODS

We report our experience with TARGIT in three centers (Australia, Germany, and the United Kingdom) between 1999 and 2008. Patients at these centers received a single radiation dose of 20 Gy to the breast tissue in contact with the applicator (or 6 Gy at 1-cm distance), as they could not be given EBRT and were keen to avoid mastectomy.

RESULTS

Eighty patients were treated with TARGIT. Reasons for using TARGIT were 21 patients had previously received EBRT, and 31 patients had clinical reasons such as systemic lupus erythematosus, motor neuron disease, Parkinson's disease, ankylosing spondylitis, morbid obesity, and cardiovascular or severe respiratory disease. Three of these patients received percutaneous radiotherapy without surgery; 28 patients were included for compelling personal reasons, usually on compassionate grounds. After a median follow-up of 38 months, only two local recurrences were observed, an annual local recurrence rate of 0.75% (95% confidence interval, 0.09%-2.70%).

CONCLUSIONS

While we await the results of the randomized trial (over 2,000 patients have already been recruited), TARGIT is an acceptable option but only in highly selected cases that cannot be recruited in the trial and in whom EBRT is not feasible/possible.

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Pubmed
Health-related quality of life after breast-conserving surgery and intraoperative radiotherapy for breast cancer using low-kilovoltage X-rays.
Journal: Annals of surgical oncology
January/10/2011
Description

BACKGROUND

Intraoperative radiotherapy (IORT) is currently being evaluated as a novel approach during breast-conserving surgery (BCS). IORT can be used either as a tumor bed boost followed by external-beam radiotherapy (EBRT) or as a single treatment. In a matched-pair study, we assessed quality of life (QoL) in 69 patients with early breast cancer treated with BCS and/or IORT and/or EBRT.

METHODS

Patients were matched for age and time since BCS. IORT was provided with 50 kV x-rays (Intrabeam) delivering 20 Gy at the applicator surface. EBRT (46 to 50 Gy in 2-Gy fractions in the IORT with EBRT group, and 56 Gy in 2-Gy fractions in the EBRT group) was initiated after completion of wound healing and/or chemotherapy. The mailed questionnaires included the European Organization for the Research and Treatment of Cancer QLQ-C30 and BR23, FACT-F, HADS, Body Image Scale, and Rosenberg Self-Esteem Scale. At 18 to 70 months' follow-up (median 47 months), all patients were disease free.

RESULTS

We found only a few differences between the three groups. There was a trend toward more pain (mean ± standard deviation; 42.8 ± 32.9 vs. 27.5 ± 34.7) and reduced QoL (57.6 ± 20.7 vs. 70.3 ± 23.9) after IORT with EBRT compared with EBRT, respectively. IORT patients reported comparable QoL (70.3 ± 23.0), and less breast symptoms and body image concerns compared to EBRT (8.6 ± 12.3 vs. 19.2 ± 23.8, and 1.7 ± 3.3 vs. 3.4 ± 4.4, respectively). IORT alone resulted in significantly fewer breast symptoms (8.6 ± 12.3; P = 0.012) and less pain (23.9 ± 24.5, P = 0.041) compared with IORT with EBRT (26.1 ± 27.6; 42.8 ± 32.9, respectively).

CONCLUSIONS

Patients with early breast cancer after BCS and IORT with or without EBRT present with comparable QoL like patients receiving EBRT without a boost. IORT patients show the lowest rate of breast symptoms.

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Pubmed
Surgical aspects in the treatment of patients with unilateral wilms tumor: a report from the SIOP 93-01/German Society of Pediatric Oncology and Hematology.
Journal: Annals of surgery
May/3/2009
Description

OBJECTIVE

To assess surgical aspects in the treatment of children with unilateral Wilms tumor based on data from the Cooperative Tumor Study SIOP 93-01 of the German Society of Pediatric Hematology and Oncology.

BACKGROUND

Although multiple international study trials exist for the treatment of nephroblastoma, the impact of surgical details and the outcome of the patients have not yet been described comparing different approaches of the trials.

METHODS

Treatment results of SIOP 93-01 of the German Society of Pediatric Hematology and Oncology were analyzed regarding frequencies of operations by surgeons and hospitals, surgical approaches, and operating subspecialties. Special attention was given to surgical complications, postoperative tumor stages and event-free survival.

RESULTS

Data sets from 757 of 1020 registered patients were received for evaluation. A unilateral Wilms tumor was observed in 512 of 757 children.Median follow-up was 4.8 years (1.2-10.7). Event-free survival rates were comparable for frequencies of operation by surgeons and hospitals, surgical approaches, and surgical specialties. Intraoperative tumor rupture rates were 12% in primarily operated patients (protocol violations) versus 3.2% inpatients after preoperative chemotherapy. There were 7% intraoperative ruptures for hospitals and surgeons performing 1 operation per year, and 3%when more than 4 operations per year were carried out. Sampling of hilar lymph nodes was often incomplete for all surgical subspecialties.

CONCLUSIONS

While the event-free survival for all groups is equal, there may be some long-term complications as a result of the more intensified therapy required for patients who suffer intraoperative ruptures. This will be defined only with longer term studies of late effects of the more intensified therapy. There is,however an increased rate of complications and ruptures associated with the use of midline laparotomy rather than a transverse or thoracoabdominal incision.

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Pubmed
Impact of radiotherapy parameters on outcome for patients with supratentorial primitive neuro-ectodermal tumours entered into the SIOP/UKCCSG PNET 3 study.
Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
October/26/2009
Description

OBJECTIVE

To evaluate the impact of radiotherapy (RT) parameters on outcome in the SIOP/UKCCSG study of pre-RT chemotherapy for Supratentorial Primitive Neuro-ectodermal Tumours.

METHODS

Sixty-two patients aged 2.9-16.6 (median 6.4 years) were eligible. Forty-eight (77%) had non-pineal sites and 14 (23%) had pineal sites. Eleven were randomized to RT alone (6) and five to pre-RT Vincristine, Etoposide, Carboplatin and Cyclophosphamide. Fifty-one were not randomized, 15 receiving RT alone and 36 receiving pre-RT chemotherapy. Craniospinal RT (CSRT) 35 Gy/21 fractions were followed by 20 Gy/12 fractions to primary tumour.

RESULTS

Mean CSRT dose was 34.7 Gy and mean total primary dose was 53.4 Gy for those who received radiotherapy. Of 30 relapses, 18 (60%) were local only and 5 (16.7%) were combined local and leptomeningeal. There was no significant impact on Overall Survival (OS) or Event-Free Survival (EFS) of surgery-RT interval for patients treated by pre-RT chemotherapy or RT alone, or duration of RT (completing within 50 days). Planning films were received for 42/54 (77.8%) patients. Fourteen (33%) had one or more targeting deviations (10 cribriform fossa, 11 base of skull). There was a statistically significant increase in the risk of recurrence for patients with cribriform fossa targeting deviations (p=0.033), but not for patients with base of skull targeting deviations (p=0.242). There was no statistically significant difference in OS (p=0.0598) or EFS (p=0.0880) for patients who had one or more targeting deviations compared to those who had none.

CONCLUSIONS

This study has not demonstrated a statistically significant impact of radiotherapy duration or targeting deviations on OS or EFS, possibly due to small patient numbers. However, multi-institutional SPNET trials should incorporate quality assurance programs including analysis of relapse pattern in relation to primary target volume coverage.

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