Spontaneous Tumor Regression Research Articles

A sequential treatment algorithm for infants with stage 4s neuroblastoma and massive hepatomegaly

Infants with 4s neuroblastoma (NB) and massive hepatomegaly have a guarded prognosis and mortality approaches 30%. We report on eight patients with 4s NB and massive hepatomegaly treated with multiple modalities. One patient had spontaneous tumor regression. Three patients had progressive disease and responded to chemotherapy. Four patients progressed despite intravenous chemotherapy, of whom two died, and two were salvaged with hepatic intra-arterial chemoembolization. Treatment of infants with stage 4s NB with massive hepatomegaly should be individualized based on disease course. A sequential approach with observation, intravenous chemotherapy, and intra-arterial chemoembolization, may improve the outcome of these infants.

'Prechronous' metastasis in clear cell renal cell carcinoma: a case report

IntroductionAlthough metastatic carcinoma in the presence of an occult primary tumor is well recognized, underlying reasons for the failure of the primary tumor to manifest are uncertain. Explanations for this phenomenon have ranged from spontaneous regression of the primary tumor to early metastasis of the primary tumor before manifestation of a less aggressive primary tumor. We report a case of 'prechronous' metastasis arising from clear cell renal cell carcinoma, where metastatic disease initially manifested in the absence of a primary renal tumor, followed by aggressive growth of the primary renal lesion.Case presentationA 43-year-old Malay man initially presented to our facility with fever and cough. He subsequently underwent surgical resection of a 9 cm right-sided lung mass found on radiological examination. Histology showed a high-grade clear cell tumor with sarcomatoid differentiation, suggestive of a metastasis from clear cell renal cell carcinoma. However, no concurrent renal lesions were noted on computed tomographic evaluation at that time. Then, four months after lung resection, he presented with a subcutaneous mass in the left loin, as well as right loin discomfort. Computed tomography scanning revealed a 10 cm right renal mass, with renal vein and inferior vena cava invasion, as well as recurrent disease in the right thorax. Histological examination of the excised subcutaneous mass revealed a high-grade carcinoma consistent with clear cell renal cell carcinoma.ConclusionsThis is the first reported case of prechronous metastasis of renal cell carcinoma, with metastatic disease manifesting prior to the development of the primary lesion. The underlying mechanism is uncertain, but our patient's case provides anecdotal support for the early dissemination model of metastasis.

Spontaneous regression of a cystic retroperitoneal tumour in young women postpartum. Report of two cases

Retroperitoneal cystic tumours are rarely found, and of these, the most common lesion is a cystic lymphangioma. We present two postpartum patients with a cystic retroperitoneal tumour which showed spontaneous regression and a review of the literature.

More Than Just Tumor Destruction: Immunomodulation by Thermal Ablation of Cancer

Over the past decades, thermoablative techniques for the therapy of localized tumors have gained importance in the treatment of patients not eligible for surgical resection. Anecdotal reports have described spontaneous distant tumor regression after thermal ablation, indicating a possible involvement of the immune system, hence an induction of antitumor immunity after thermoinduced therapy. In recent years, a growing body of evidence for modulation of both adaptive and innate immunity, as well as for the induction of danger signals through thermoablation, has emerged. Induced immune responses, however, are mostly weak and not sufficient for the complete eradication of established tumors or durable prevention of disease progression, and combination therapies with immunomodulating drugs are being evaluated with promising results. This article aims to summarize published findings on immune modulation through radiofrequency ablation, cryoablation, microwave ablation therapy, high-intensity focused ultrasound, and laser-induced thermotherapy.

Long-term Outcome After Resection of Intraspinal Ependymomas: Report of 86 Consecutive Cases

To evaluate progression-free survival, overall survival (OS) and long-term clinical outcome in a consecutive series of 86 patients with intraspinal ependymomas. Medical charts were retrospectively reviewed. Surviving patients voluntarily participated in a clinical history and physical examination that focused on neurological function and current tumor status. Follow-up data are nearly 100% complete; mean follow-up time was 82 months. Eighty-five patients (99%) had surgery as a first-line treatment; 14 (17%) of these patients received adjuvant radiotherapy. Of the 85 patients who underwent primary surgery, gross total resection was performed in 60 patients (71%) and subtotal resection in 25 patients (29%). Ten-year progression-free survival rate was 75%; 5-year OS, 97%; and 10-year OS, 91%. Reduced preoperative neurological function and older age at diagnosis were significantly associated with increased risk of death. At follow-up, spontaneous regression of residual tumor after primary surgery may have occurred in 7 of 19 patients (37%). More than 75% of patients had neurological function compatible with an independent life at follow-up. Good preoperative neurological function was significantly associated with favorable outcome. It was not possible to evaluate the effect of radiotherapy on progression-free survival and OS. Gross total resection remains the optimal treatment for patients with spinal ependymoma. Patients should be monitored with a clinical examination and magnetic resonance imaging at regular intervals up to 10 years after surgery.

Spontaneous regression of malignant tumors: Importance of the immune system and other factors (Review).

It has been established that malignant tumors as well as metastases, of almost all histological types, can regress spontaneously although certain histological types regress more frequently than others. Various causes thereof include apoptosis, the immune system and particular conditions of the tumor microenvironment. The action of the genome in the regression of tumors is not clear, but some data, apart from those of apoptosis, support its involvement. The hypothesis that the immune system exhibits variations in efficacy, even to a marked extent, in determining partial or total regression of tumors appears to be plausible. Such variable efficacy may be supported by blockage of growth and the proliferation of cancer cells at the level of the tumor microenvironment, the intervention of various factors such as inhibitors of metalloproteinases and angiogenesis, and the absence or scarcity of particular proteins. The consequence of such a blockage would be a relative increase in the number of natural killer cells and other elements involved in the immune system in relation to the number of circulating cancer cells in the blood. A relative increase in the number of elements of the immune system is more effective than an absolute increase, since an absolute increase is able to stimulate, as frequently occurs for feedback in biological equilibria, inhibitor receptors that reduce the efficacy of the same elements (mainly natural killer and CD8(+) T cells). Such an increase in the efficacy of the immune system can lead, at least in certain cases, to the so-called spontaneous regression of malignant tumors. Clinical practice has demonstrated that metastases are less frequent in patients with renal carcinoma undergoing hemodialysis compared with patients with renal carcinoma not on hemodialysis. This finding can be interpreted, in correlation with the blockage of cancer cells in tissues, as a consequence of a partial blockage of metastatic cancer cells at the level of the dialytic membrane, with a subsequent increase in the relative efficacy of the immune system.

Identification of Carbonic Anhydrase I Immunodominant Epitopes Recognized by Specific Autoantibodies Which Indicate an Improved Prognosis in Patients with Malignancy after Autologous Stem Cell Transplantation

This work employs an epitope mapping of carbonic anhydrase (CA), isoform I (CA I), for detection of the main immunodominant epitopes. Our interest has arisen from an observed spontaneous tumor regression in patients who developed an aplastic anemia type syndrome after a high-dose therapy with autologous stem cell transplantation and whose sera contained high titer of anti carbonic anhydrase (anti-CA) autoantibodies. There are many indications that the presence of these autoantibodies may provide significant survival benefit for the patients. Western blot analysis confirmed strong immunoreactivity of the patients' sera with several CA isoforms and the CA I has been selected for our study as a highly abundant and widely distributed isoform. The applied analytical approach consists of specific fragmentation of CA I protein followed by immunospecific isolation of peptides reacting with polyclonal anti-CA I autoantibodies of patients in spontaneous remission. We improved the standard epitope mapping schema by incorporating the benefits of magnetic carriers and biomagnetic separation techniques. Mass spectrometry has been applied for detection and identification of epitopes and the acquired results were verified by bioinformatic tools. The candidate epitopes of CA I (NVGHS, DGLAV, SSEQL, and SLKPI) are discussed herein as potential therapeutic targets. This work highlights the usefulness of the epitope mapping technique based on magnetic microspheres for effective and rapid determination of immunodominant epitopes of the target protein.

Cytosolic Phospholipase A2 and Lysophospholipids in Tumor Angiogenesis

BackgroundLung cancer and glioblastoma multiforme are highly angiogenic and, despite advances in treatment, remain resistant to therapy. Cytosolic phospholipase A2 (cPLA2) activation contributes to treatment resistance through transduction of prosurvival signals. We investigated cPLA2 as a novel molecular target for antiangiogenesis therapy.MethodsGlioblastoma (GL261) and Lewis lung carcinoma (LLC) heterotopic tumor models were used to study the effects of cPLA2 expression on tumor growth and vascularity in C57/BL6 mice wild type for (cPLA2α+/+) or deficient in (cPLA2α−/−) cPLA2α, the predominant isoform in endothelium (n = 6–7 mice per group). The effect of inhibiting cPLA2 activity on GL261 and LLC tumor growth was studied in mice treated with the chemical cPLA2 inhibitor 4-[2-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]-ethoxy]benzoic acid (CDIBA). Endothelial cell proliferation and function were evaluated by Ki-67 immunofluorescence and migration assays in primary cultures of murine pulmonary microvascular endothelial cells (MPMEC) isolated from cPLA2α+/+ and cPLA2α−/− mice. Proliferation, invasive migration, and tubule formation were assayed in mouse vascular endothelial 3B-11 cells treated with CDIBA. Effects of lysophosphatidylcholine, arachidonic acid, and lysophosphatidic acid (lipid mediators of tumorigenesis and angiogenesis) on proliferation and migration were examined in 3B-11 cells and cPLA2α−/− MPMEC. All statistical tests were two-sided.ResultsGL261 tumor progression proceeded normally in cPLA2α+/+ mice, whereas no GL261 tumors formed in cPLA2α−/− mice. In the LLC tumor model, spontaneous tumor regression was observed in 50% of cPLA2α−/− mice. Immunohistochemical examination of the remaining tumors from cPLA2α−/− mice revealed attenuated vascularity (P ≤ .001) compared with tumors from cPLA2α+/+ mice. Inhibition of cPLA2 activity by CDIBA resulted in a delay in tumor growth (eg, LLC model: average number of days to reach tumor volume of 700 mm3, CDIBA vs vehicle: 16.8 vs 11.8, difference = 5, 95% confidence interval = 3.6 to 6.4, P = .04) and a decrease in tumor size (eg, GL261 model: mean volume on day 21, CDIBA vs vehicle: 40.1 vs 247.4 mm3, difference = 207.3 mm3, 95% confidence interval = 20.9 to 293.7 mm3, P = .021). cPLA2 deficiency statistically significantly reduced MPMEC proliferation and invasive migration (P = .002 and P = .004, respectively). Compared with untreated cells, cPLA2α−/− MPMEC treated with lysophosphatidylcholine and lysophosphatidic acid displayed increased cell proliferation (P = .011) and invasive migration (P < .001).ConclusionsIn these mouse models of brain and lung cancer, cPLA2 and lysophospholipids have key regulatory roles in tumor angiogenesis. cPLA2 inhibition may be a novel effective antiangiogenic therapy.

Spontaneous regression of thoracic malignancies

Clinicians are frequently questioned by patients about the possibility of spontaneous regression of tumors. Although there are many reports and a few case series documenting spontaneous regression, there is concern that these cases may not represent true regression. Using specific criteria, we attempted to determine the incidence and types of thoracic malignancy most likely to regress spontaneously. We used a PubMed search of the phrase "spontaneous regression of thoracic lesions" reported from 1951 to December 2008. Using a modified Everson and Cole criterion we developed to define spontaneous regression, this search was refined for true spontaneous regression of primary and metastatic thoracic malignancies. Only 5 cases in the literature involved spontaneous regression of a primary thoracic malignancy. These include pleural mesothelioma, primary lung cancer and adenoid cystic carcinoma. 71 cases involved true spontaneous regression of metastatic thoracic neoplasms, of which 5 cases showed regression of the primary extrapulmonary tumors along with the pulmonary metastasis. Thoracic metastasis from renal cell carcinoma was the most common malignancy found to regress spontaneously. Spontaneous regression of primary thoracic malignancy is rare. Renal cell carcinoma accounts for most reported cases.

Multimodal treatment of nodal localizations from Merkel cell carcinoma with no identifiable primary site and distant metastases.

e19020 Background: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. In sporadic cases nodes represent the only site of disease, anecdotally due to a spontaneous regression of the primary cutaneous tumor. Besides differential diagnosis primary/metastatic nodal localization is debated. No standard treatment exists in this setting. We report our multimodal management. Methods: Among patients with MCC examined at European Institute of Oncology of Milan between October 1995 and March 2009, we selected those with nodal involvement without evidence of primary tumor. Then we considered: histological diagnosis at IEO, no visceral sites of disease, staging with CT ± fluorodeoxyglucose (FDG) positron emission tomography (PET) ± somatostatin receptor scintigraphy (SRS), multidisciplinary discussion. We evaluated staging, multimodality, time to progression (TTP), median overall survival (mOS). Results: Among a total of 83 patients 28 had the above mentioned characteristics. All patients were staged with CT. A FDG-PET was positive for staging in 14/17 patients, and SRS in 12/17. Concordance FDG-PET/SRS was positive in 8 and negative in 1 cases. In 2 cases PET positive/SRS negative occurred. Thirteen patients underwent excisional biopsy, without lymphadenectomy. Six received chemoradiation, 3 chemotherapy, 1 chemo-biotherapy, 1 radiotherapy, 2 no treatment. Fifteen patients underwent lymphadenectomy, 7 with adjuvant chemoradiation, 4 chemotherapy, 1 radiation, 1 with neoadjuvant chemotherapy, 1 no further treatment, and 1 too early. With 22 months median follow-up median TTP was 17 months (95%CI: 7-NE). Median OS was 29 months (95%CI: 15-NE). TTP and mOS for patients underwent lymphadenectomy were not reached vs. 9 months (95%CI: 4-NE; p = 0.35) and 29 months (95%CI: 11.7, NE; p = 0.34) for patients without lymphadenectomy, respectively. Conclusions: In patients with nodal localizations of MCC without evidence of primary tumor and distant metastases lymphadenectomy improved TTP and mOS. FDG-PET for staging seems to be more accurate than SRS. The role of a multimodal therapeutic strategy should be studied in prospective trials. No significant financial relationships to disclose.

High level of apoptosis and low AKT activation in mass screening as opposed to standard neuroblastoma

Neuroblastoma is a paediatric solid tumour with a poor outcome except in children <1 year old. Based on catecholamine urinary excretion, mass screening (MS) programmes have been organized but failed to decrease the mortality of this tumour. To test the hypotheses of a spontaneous maturation/differentiation or regression, the levels of poly (ADP-ribose) polymerase (PARP)-1, an early apoptosis marker, of PhosphoAKT, a major apoptosis inhibitor, and of maturation/differentiation were compared in standard and in MS neuroblastomas. We performed a case-control study of 55 primary tumours and 21 metastases of MS neuroblastomas. Matched controls were standard unscreened neuroblastomas and were paired according to age, stage, and MYCN amplification. The tumours were included in tissue microarrays. Immunohistochemical staining was performed using antibodies against, AKT, phosphoAKT, TRKB and PARP-1. The expression of PARP-1 and that of phosphoAKT were significantly higher in standard than in MS neuroblastomas independently of age and stage of the tumour. PhosphoAKT and PARP-1 expression was significantly correlated in both tumours. These data suggest that the better prognosis of patients with MS neuroblastomas compared with classical neuroblastomas was secondary to spontaneous tumour regression mediated by higher levels of apoptosis associated with low activation of AKT.

Lung Tumor Development and Spontaneous Regression in Lambs Coinfected With Jaagsiekte Sheep Retrovirus and Ovine Lentivirus

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring and experimentally inducible lung cancer of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The first aim of this study was to monitor the development of OPA with minimally invasive, real-time observations of animals experimentally infected with JSRV as well as ovine lentivirus (maedi-visna virus). Worldwide, simultaneous infection of sheep with these 2 retroviruses is a common occurrence, naturally and experimentally; consequently, the lung tumor homogenates used as inocula contained both viruses. Following inoculation, computed tomography was used to detect tumor nodules early, before the onset of clinical signs, and to monitor tumor advancement. However, not only was OPA disease progression observed, but the apparent spontaneous regression of OPA was witnessed. In fact, regression was more common than progression following JSRV inoculation of neonatal lambs. Immune responses were detected, particularly involving CD3(+) T cells and the production of antibodies against JSRV that may mediate the spontaneous regression of JSRV-induced OPA. The second aim of this study was to determine whether OPA tumors harbor genetic alterations similar to those found in human lung adenocarcinoma. No mutations were found in the tyrosine kinase domain of the epidermal growth factor receptor, KRAS codons 12 and 13, or the DNA-binding domain of p53 in tumor DNA from naturally occurring and experimentally-induced OPA cases. Overall, the genetic profile combined with the disease development data provides further important characterization of OPA and describes, for the first time, spontaneous regression of OPA tumors in experimentally infected sheep.

Spontaneous regression of vestibular schwannomas after resection of contralateral tumor in neurofibromatosis Type 2

The authors report on 2 patients with bilateral vestibular schwannomas (VSs) who underwent unilateral surgical tumor removal. One patient was followed up for 4 years, the other for 9; in both cases, the contralateral VS regressed markedly without any additional treatment during the follow-up period. Serial MR imaging was performed to monitor the untreated tumor, which in both cases involved the only hearing ear. The tumors were assessed volumetrically. The contralateral tumors appeared to enlarge mildly at initial follow-up and then, with no treatment, regressed (to 23% of the original maximum volume in Case 1 and to 15% of the original maximum in Case 2). The largest posterior fossa diameter decreased from 30.1 mm to 18.6 mm in Case 1 over 4 years and from 27 mm to 16 mm over 8 years in Case 2. Hearing declined only mildly during follow-up in both patients. These cases demonstrate the first well-documented, long-term, spontaneous VS regressions in patients with neurofibromatosis Type 2. They underline the importance of careful observation of VS involving the only hearing ear in the management of bilateral VS to determine the natural growth pattern of the tumors. The mechanism of the dramatic spontaneous tumor regression is uncertain.

Clinicopathological Study of Regressed Testicular Tumors (Apparent Extragonadal Germ Cell Neoplasms)

Testicular germ cell tumors sometimes regress spontaneously and manifest exclusively by metastasis. We report our experience with extragonadal germ cell tumors of probable testicular origin to study the frequency of this entity, and clinical, ultrasound and histopathological correlations in a series of patients. A retrospective 16-year review of 1.2 million inhabitants in Spain revealed 17 with regressed testicular tumors treated at a total of 4 institutions. We analyzed clinical information, ultrasound features and histopathological characteristics of testicular lesions and metastasis, and highlight the main findings. A primary testicular origin was confirmed in all cases. This entity is more common than initially suspected since it accounts for 4% of consecutive germ cell tumors. Clinical manifestations varied according to metastatic site with an abdominal palpable mass (47% of cases), loin pain (35%) and transient testicular pain (29%) the most common complaints. No evidence of testicular neoplasms was found on physical examination in any case. Metastasis histology was nonseminomatous in 53% of cases, pure seminoma in 29% and mixed in 18%. The most common ultrasound features were calcifications in 65% of cases, hyperechogenic linear images in 59% and hypoechogenic nodular areas in 41%. Histological findings consisted of fibrotic areas in 100% of cases, hemosiderin deposits in 65%, seminiferous tubule atrophy in 59% and psammoma bodies in 29%. In testicular parenchyma or spermatic chord intratubular neoplasms and viable tumor foci were also noted (47% and 41% of cases, respectively). Spontaneous regression of a germ cell testicular tumor should be considered in each patient with extragonadal germ cell neoplasms. Ultrasound diagnosis of and surgical treatment for these primary testicular tumors appear critical to prevent relapse because residual disease develops in a significant proportion of cases.

Spontaneous regression of natural killer cell lymphoma

Spontaneous tumour regression is extremely rare in aggressive lymphoma. A case of natural killer (NK) cell lymphoma with cutaneous manifestation showed an indolent clinical course, and the relapsed nodular lesion...

Malignant pleural mesothelioma with long-term tumor disappearance of a local relapse after surgery: a case report

IntroductionThere have been few reports of spontaneous regression of malignant pleural mesothelioma, but the mechanism for this is unknown. We present a case report on a patient with malignant pleural mesothelioma showing apparent tumor disappearance in a local relapse after surgery.Case presentationA 73-year-old man presented with malignant pleural mesothelioma in the right thoracic cavity. A pleurectomy was performed, and as expected, the tumor locally relapsed with increasing chest pain. However, the symptoms suddenly improved while the tumor was apparently reduced, and spontaneous tumor regression was initially considered. The patient confessed that he had self-administered a mushroom extract with alternative parasympathetic nerve stimulation therapy thereafter. The complete disappearance of the tumor was clinically achieved during a 29-month follow-up with continuing self-treatment.ConclusionThis is the first report describing a malignant pleural mesothelioma patient in Japan showing long-term complete disappearance of a local relapse after surgery. This event was a tumor regression possibly due to an immunological effect of combined complementary and alternative therapy.

Tumor vaccine therapy for melanoma: review of literature

The phenomenon of tumor spontaneous regression of many patients with melanoma makes re-searchers pay much attention to the innate immunogenicity of melanoma.It's also supported by serveral manifestations of histo- logical observation, Correspondingly, patients with Breast Medullary Carcinoma or skin Maligant Melanoma who have an infiltration of lymphocytes get better prognosis. Moreover.it' s demonstrated that cytokines play an important role in such regulation of antitumor im- munological reponse. All above imply that there is active anti- tumor immunological response in the body and en- lighten researchers to innitiate a series of studies on tumor vaccine using the melanoma as a theraputic mod- el. This article reviews the tumor vaccine therapy for melanoma on the advantage and disadvantage of its main types and relative clinicalo trials. Key words: Cancer vaccine; Melanoma

Burned-out testicular tumor with retroperitoneal lymph node metastasis: a case report

IntroductionA burned-out seminoma of the testis is an exceptionally rare clinical entity, with few reports found in the literature.Case presentationA case of burned-out tumor of the testis in a 31-year-old man is reported. The tumor presented as a retroperitoneal mass with histological characteristic of a seminoma. The testes on clinical examination were normal, and a suspicious lesion in the scrotum was only identified after ultrasound. Incision of the abdominal mass was decided, followed by orchectomy. Histological examination of the testis revealed a suspicious lesion with characteristics of spontaneous regression of germ cell tumors.ConclusionWe describe one of very few cases worldwide, where spontaneous regression of a primary testicular tumor occurred after demonstration of retroperitoneal lymph node metastasis, a phenomenon known as burned-out seminoma, which is hard to recognize and incompletely characterized by physicians.

A Case of Partial Spontaneous Regression of Non-Small Cell Lung Cancer

Spontaneous regression is extremely rare in lung cancer and this in spite of its global high incidence. So far, less than 30 such cases have been reported in the literature. We report here on the case of a 68-year-old man who had the diagnosis of adenocarcinoma and in absence of any medical therapy, he had a partial spontaneous regression of tumor.

Spontaneous Tumour Regression

Spontaneous regression of malignant tumours is an extremely rare phenomenon. However, it is reported in virtually in all types of human cancer, although the greatest numbers of cases are reported in patients with neuroblastoma, renal carcinoma to mention a few. The induction of spontaneous regression involves multiple mechanisms which may either be differentiation, apoptosis and genetic crisis. But better understanding of the process of spontaneous regression may offer the possibility of improved methods of treating and preventing cancer.