Evidence Of Tumor Regrowth Research Articles

Integrating surgical intervention and watch-and-wait approach in dMMR metastatic rectal cancer with pembrolizumab: a case report

BackgroundTreating rectal cancer presents challenges due to postoperative complications and reduced quality of life (QOL). Recent evidence supports the watch-and-wait (WW) approach for patients with a clinical complete response (cCR) following preoperative treatment. In this report, we discuss a case of metastatic rectal cancer with deficient mismatch repair (dMMR) treated successfully with pembrolizumab.Case presentationA 47-year-old male with dMMR rectal cancer and a single liver metastasis underwent treatment with pembrolizumab as neoadjuvant therapy. After 10 courses, the rectal lesion achieved cCR, prompting the selection of the WW approach. The liver metastasis showed significant shrinkage; however, the presence of a residual tumor was suspected, leading to a metastasectomy. A pathological complete response (pCR) was confirmed via histological examination. During a 24-month follow-up, there was no evidence of tumor regrowth, local recurrence, or distant metastasis.ConclusionsThe WW strategy is increasingly accepted for patients achieving cCR after preoperative treatment. While pCR in dMMR rectal cancer patients treated with immune checkpoint inhibitors (ICIs) has been documented, accurately predicting pCR from imaging remains challenging. This case illustrates that integrating ICI therapy, surgical interventions, and the WW approach can effectively achieve both oncological safety and improved QOL in the treatment of dMMR metastatic rectal cancer.

Can Ethanol Ablation Achieve Durable Control of Neck Nodal Recurrences in Adults With Stage I Papillary Thyroid Cancer?

Results of ethanol ablation (EA) for controlling neck nodal metastases (NNM) in adult patients with papillary thyroid carcinoma (APTC) beyond 6 months have rarely been reported. We now describe outcome results in controlling 71 NNM in 40 node-positive stage I APTC patients followed for 66 to 269 months. All 40 patients were managed with bilateral thyroidectomy and radioiodine therapy and followed with neck ultrasound (US) for >48 months after EA. Cumulative radioiodine doses ranged from 30 to 550 mCi; pre-EA 27 patients (67%) had 36 additional neck surgeries. Cytologic diagnosis of PTC in 71 NNM selected for EA was confirmed by US-guided biopsy. EA technique and follow-up protocol were as previously described. The 40 patients had 1 to 4 NNM; 67/71 NNM (94%) received 2 to 4 ethanol injections (total median volume 0.8 cc). All ablated 71 NNM shrank (mean volume reduction of 93%); nodal hypervascularity was eliminated. Thirty-eight NNM (54%) with initial volumes of 12-1404 mm3 (median 164) disappeared on neck sonography. Thirty-three hypovascular foci from ablated NNM (pre-EA volume range 31-636 mm3; median 147) were still identifiable with volume reductions of 45% to 97% observed (median 81%). There were no complications and no postprocedure hoarseness. Final results were considered to be ideal or near ideal in 55% and satisfactory in 45%. There was no evidence of tumor regrowth after EA. Our results demonstrate that for patients with American Joint Committee on Cancer stage I APTC, who do not wish further surgery or radioiodine, and are uncomfortable with active surveillance, EA can achieve durable control of recurrent NNM.

Engineered Ultrasmall Nanoparticle Drug-Immune Conjugates with "Hit and Run" Tumor Delivery to Eradicate Gastric Cancer.

Despite advances by recently approved antibody-drug conjugates in treating advanced gastric cancer patients, substantial limitations remain. Here, several key obstacles are overcome by developing a first-in-class ultrasmall (sub-8-nanometer (nm)) anti-human epidermal growth factor receptor 2 (HER2)-targeting drug-immune conjugate nanoparticle therapy. This multivalent fluorescent core-shell silica nanoparticle bears multiple anti-HER2 single-chain variable fragments (scFv), topoisomerase inhibitors, and deferoxamine moieties. Most surprisingly, drawing upon its favorable physicochemical, pharmacokinetic, clearance, and target-specific dual-modality imaging properties in a "hit and run" approach, this conjugate eradicated HER2-expressing gastric tumors without any evidence of tumor regrowth, while exhibiting a wide therapeutic index. Therapeutic response mechanisms are accompanied by the activation of functional markers, as well as pathway-specific inhibition. Results highlight the potential clinical utility of this molecularly engineered particle drug-immune conjugate and underscore the versatility of the base platform as a carrier for conjugating an array of other immune products and payloads.

Engineered Ultrasmall Nanoparticle Drug‐Immune Conjugates with “Hit and Run” Tumor Delivery to Eradicate Gastric Cancer

AbstractDespite advances by recently approved antibody‐drug conjugates in treating advanced gastric cancer patients, substantial limitations remain. Here, several key obstacles are overcome by developing a first‐in‐class ultrasmall (sub‐8‐nanometer (nm)) anti‐human epidermal growth factor receptor 2 (HER2)‐targeting drug‐immune conjugate nanoparticle therapy. This multivalent fluorescent core–shell silica nanoparticle bears multiple anti‐HER2 single‐chain variable fragments (scFv), topoisomerase inhibitors, and deferoxamine moieties. Most surprisingly, drawing upon its favorable physicochemical, pharmacokinetic, clearance, and target‐specific dual‐modality imaging properties in a “hit and run” approach, this conjugate eradicated HER2‐expressing gastric tumors without any evidence of tumor regrowth, while exhibiting a wide therapeutic index. Therapeutic response mechanisms are accompanied by the activation of functional markers, as well as pathway‐specific inhibition. Results highlight the potential clinical utility of this molecularly engineered particle drug‐immune conjugate and underscore the versatility of the base platform as a carrier for conjugating an array of other immune products and payloads.

Anaplastic Sarcoma and Sertoli Cell Tumor in a Central Bearded Dragon (Pogona vitticeps)

A five-year-old male central bearded dragon (Pogona vitticeps) was presented for investigation of blood in the voided urates. A small cutaneous mass was detected in the gular region, but clinical examination was otherwise unremarkable. Fecal parasitology was negative. Initially, further diagnostics were declined, and antimicrobial treatment was initiated. At re-examination one month later, the gular mass had increased in size and an additional mass was detected within the celomic cavity. Both masses were surgically excised and diagnosed by histopathology as a high-grade anaplastic sarcoma (gular mass), resembling a histiocytic sarcoma, and a Sertoli cell tumor (coelomic mass). Neither of these have been previously reported in the central bearded dragon. Twenty months post-surgery, the lizard remains well with no recurrence of clinical signs or evidence of tumor re-growth.

Subconjunctival hibernoma in a dog

A 10-year-old, castrated male, German Shepherd mixed-breed dog was presented to Kansas State University Veterinary Health Center for evaluation of a subconjunctival swelling in the ventral fornix of the left orbit. The owner elected to pursue excision of the mass 2 years after initial consultation following a sudden change in the size and color of the lesion. An excisional biopsy was performed, and the mass along with its associated capsule were submitted to the Comparative Ocular Pathology Laboratory of Wisconsin for histopathologic evaluation, which confirmed the diagnosis of a hibernoma. Fourteen months following excision, the patient showed no evidence of tumor regrowth.

Abstract C206: High antitumor complete response rate to Namitecan (ST1968) in preclinical model of pediatric sarcomas.

Abstract Namitecan (ST1968), a new water-soluble camptothecin analogues, exhibits an improved pharmacological profile over conventional camptothecins. This molecule was selected for clinical development on the basis of preclinical evidence of superior efficacy than Topotecan or irinotecan and of its favorable therapeutic index. Namitecan has shown an high rate of sustained disease control in patients with solid tumors in Phase I, as predicted by preclinical data. Given the interest for the irinotecan treatment of pediatric tumors, this study was designed to explore the efficacy of Namitecan in preclinical models of pediatric sarcomas (TC-71, RH30, RD/TE671, A204 and U2OS cell lines). Namitecan showed an impressive antitumor efficacy in 4/5 of the tested xenograft sarcoma models at doses ranging 15–30 mg/kg given i.v. in a q4d×3w, as documented by the rate of complete tumor regression without evidence of tumor regrowth at the end of the experiments (around 120 days). The outstanding Namitecan activity against pediatric sarcoma xenografts is emphasized by the observation that complete tumor regression could be achieved also by the dose of 15 mg/kg (i.e., ½ MTD) allowing the use of well-tolerated effective doses in clinical therapy. Moreover, the i.v. administration of Namitecan resulted in a high and persistent drug accumulation in TC-71 tumor xenograft, which could account for the good therapeutic index. Since no correlation could be found between in vitro growth inhibitory activity and in vivo antitumor efficacy, it is likely that other in vivo effects may contribute to the drug antitumor efficacy. Indeed, in the RD/TE671 rhabdomyosarcoma model, we found that Namitecan activity was associated with a marked antiangiogenic effect, which was consistent with the down regulation of proangiogenic factors, including VEGF, bFGF and CCL-2, an angiogenesis chemokine mediator. Furthermore, we found that HIF-1α expression is strongly down regulated in our cellular models following treatment with Namitecan. These findings are in line with a supposed antiangiogenic activity of camptothecins likely to affect proliferation and migration of endothelial cells and down regulation of angiogenic factors and the known ability of Topoisomerase I inhibitors to inhibit the translation of HIF-1α protein which is a transcriptional activator of VEGF. In conclusion, the available evidence supports that inhibition of angiogenesis contributes to the responsiveness of pediatric sarcomas to Namitecan, according to the role of angiogenesis in malignant behavior of these tumor types. Thus, the impressive efficacy of Namitecan against pediatric sarcoma may reflect: i) direct cytotoxic effects on tumor cells, as a result of persistent tumor accumulation of the drug and high topo I expression, ii) inhibition of angiogenesis and iii) a favorable in vivo drug distribution. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C206.

Neuroblastoma: An unusual diagnosis for a pediatric retropharyngeal mass

Objective: To describe the diagnosis and management of a one-year-old male who presented with stridor due to a retropharyngeal neuroblastoma. Method: Retrospective case review. Results: The retropharyngeal neuroblastoma was surgically debulked in the operating room and the stridor improved significantly. The patient continues to be followed with serial MRIs and has no evidence of tumor regrowth or metastasis to this date. Conclusion: Neuroblastoma should be considered in the differential diagnosis of a pediatric retropharyngeal mass. If 50% of the tumor is debulked, the patient can be treated conservatively unless aerodigestive symptoms do not resolve or metastasis is present.

Cytologic and immunohistochemical characterization of a lung carcinoid in a dog

An 11-year-old neutered male Yorkshire Terrier was presented to the Haemaru Referral Animal Hospital with a history of unresponsive tracheal collapse and an incidental finding of a lung nodule in the left caudal lung lobe on radiography. Thorough physical examination and imaging studies revealed no other masses. Cytologic examination of C-arm mobile fluoroscopy-guided fine-needle aspirates revealed numerous free nuclei and a low number of small round cells with moderate to abundant pale basophilic cytoplasm. Some cells contained indistinct basophilic granules in their cytoplasm, and extracellular pink material was noted. A caudal lung lobectomy was performed, and histologic evaluation of the mass revealed round to polygonal cells with abundant eosinophilic granular cytoplasm and round nuclei with mild anisokaryosis and 0-3 mitotic figures per high-power field. Cells were arranged in packets separated by fine fibrovascular stroma, suggestive of a pulmonary neuroendocrine neoplasm, specifically a carcinoma/carcinoid. The cells were immunoreactive for chromogranin A and neuron-specific enolase, and negative for cytokeratin, synaptophysin, calcitonin, thyroglobulin, parathyroid hormone, CD79a, light lambda, and vimentin. With these findings the tumor was diagnosed as a primary lung carcinoid. Eleven months after resection, there was no evidence of tumor regrowth or metastasis. The absence of necrosis, few mitotic figures, minimal pleomorphism, and benign behavior of this tumor resembled those of a typical carcinoid in humans.

Predictors of remission of hyperprolactinaemia after long‐term withdrawal of cabergoline therapy

Remission rates of 76, 69.5 and 64.3% have been reported in patients with nontumoural hyperprolactinaemia (NTH), microprolactinoma and macroprolactinoma, respectively, 2-5 years after cabergoline (CAB) withdrawal. To report the estimated recurrence rate at 24-96 months after CAB withdrawal and indicate predictors of disease remission. Observational, analytical, prospective. Of 381 previously untreated de novo patients with hyperprolactinaemia, 221 (58%) (173 women, 48 men; 27 with NTH, 115 with micro-, and 79 with macroprolactinoma) were studied. Using multiple regression analysis the diagnostic accuracy of nadir PRL levels (t = 7.6, P < 0.0001) and nadir maximal tumour diameter at CAB withdrawal (t = 3.9, P < 0.001) was analysed using receiver operating characteristic (ROC) curves. The recurrence of hyperprolactinaemia was 25.9, 33.9 and 53.1% in patients with NTH, micro- or macroprolactinoma, respectively. To predict the last PRL level after withdrawal, the optimum cut-off of nadir PRL levels at withdrawal was 162 mU/l (5.4 microg/l) [sensitivity (95% CI) 76% (67-84%), specificity 65% (51-77%)] and that of nadir maximal tumour diameter was 3.1 mm [sensitivity 52% (41-63%), specificity 86% (79-91%)]. The patients achieving both nadir PRL levels </= 162 mU/l and maximal tumour diameter </= 3.1 mm (n = 111) at CAB withdrawal had a significantly lower Kaplan-Meier estimate of recurrence of hyperprolactinaemia (20%) at 24-96 months than those who did not fulfil any of these criteria [(n = 38) 90%; P < 0.0001]. Patients achieving nadir PRL levels </= 162 mU/l (n = 26) or maximal tumour diameter </= 3.1 mm during CAB treatment (n = 46) had an estimated recurrence rate of hyperprolactinaemia of 50 and 56%, respectively. Persistent remission of hyperprolactinaemia without any evidence of tumour re-growth after 24-96 months of CAB withdrawal occurred in the majority of patients with NTH and microprolactinoma and in about half of those with macroprolactinoma. Nadir PRL levels and maximal tumour diameter at CAB withdrawal of </= 162 mU/l and </= 3.1 mm predicted remission of hyperprolactinaemia in 80% of patients.

Infiltrative Lipoma in a Blue-Crowned Conure (Aratinga acuticaudata)

A 14-year-old blue-crowned conure (Aratinga acuticaudata) of unknown sex was brought to the hospital with a 3-week history of straining and vocalizing during defecation. Physical examination revealed blood and urate staining on feathers around the cloaca. A 2.5-cm subcutaneous swelling was palpated along the midline of the caudoventral abdomen. During surgical exploratory, a subcutaneous soft-tissue mass was found, which extended through the body wall musculature and into the coelomic cavity. The abnormal tissue was adhered to the cloacal serosa, causing deviation of the cloaca caudally and ventrally. The mass was excised and submitted for histopathology, and the histopathologic diagnosis was infiltrative lipoma. The surgical incision healed uneventfully, and no evidence of tumor regrowth was apparent 7 months after surgery. This is the first documented case of infiltrative lipoma in a bird.

Distribution of radioactivity and metabolite profiling in tumour and plasma following intravenous administration of a colchicine derivative (14C-ZD6126) to tumour-bearing mice

The main aim of the study was to investigate the distribution of radioactivity in the tissues and tumours using quantitative whole-body autoradiography (QWBA), together with a more detailed investigation of plasma and tumour samples, following administration of a single intravenous dose at 200 mg kg−1 of 14C-ZD6126 to mice bearing subcutaneous Hras5 tumour xenografts. The study also included an assessment of tumour necrosis following administration of a single intravenous dose of non-labelled ZD6126 at 200 mg kg−1. QWBA analysis showed that drug-related material was widely distributed to the tissues and tumour. In the majority of tissues, concentrations of radioactivity were highest at 15 min and declined rapidly thereafter. The tumour-to-plasma ratio was 0.6:1 at 0.25 h and increased to 6:1 at 48 h, indicating that drug-related material persisted in the tumour longer than in plasma. ZD6126, a phosphate ester, is rapidly hydrolysed to ZD6126 phenol, the active metabolite. The major metabolite in plasma (36% of the sample radioactivity) and all tumour samples (58–83% of the sample radioactivity) was confirmed as ZD6126 phenol. Extensive tumour necrosis was noted by 24 h, which was still evident at 48 h, although there was some evidence of tumour regrowth.

Re-irradiation and hyperthermia for recurrent breast cancer in the orbital region: a case report

Based on the good results of re-irradiation plus hyperthermia in breast cancer recurrences on the chest wall, it was decided to offer similar treatment to a patient with recurrent metastatic breast cancer in the orbital region. A female patient was diagnosed in 1997 with breast cancer stage T4N0M0. She was treated with six neo-adjuvant chemotherapy courses and mastectomy, followed by hormonal treatment. In December 1998, she was diagnosed with metastatic disease in the medial upper quadrant of the left orbit. This was excised, followed by 40 Gy radiotherapy. Nine months later, the tumour had recurred in the left orbit at the margin of the radiotherapy field. This again was treated with surgery, followed by 30 Gy radiotherapy. Two months thereafter, the eyelid tumour progressed and hormonal therapy was changed, without an effect on the eyelid tumour. Screening gave no evidence of tumour activity elsewhere. The patient preferred treatment with re-irradiation plus hyperthermia to a surgical approach. Eight fractions of 4 Gy were given in 4 weeks, combined with once weekly hyperthermia. One week after treatment, the tumour had regressed completely. The patient died 22 months following treatment. Until last follow-up, a few weeks before death, the patient mentioned a dry left eye for which she used eyedrops, an unchanged vision and no further difficulties. On examination, there was epilation of the eyelids, a slight conjunctival oedema, no subcutaneous fibrosis and no evidence of tumour regrowth. For this patient, a surgical approach would have resulted in loss of the left eye. Toxicity of re-irradiation plus hyperthermia might lead to either a loss of vision or a delayed loss of her left eye due to treatment-induced toxicity. The chosen local treatment resulted in a very good palliative effect, which lasted for the patient’s remaining lifetime of 22 months.

Surgical approaches and strategies for skull base chordomas

The management of chordomas involving the skull base continues to present a number of treatment-related problems. Recently, both radical resection and charged-particle irradiation or stereotactic radiosurgery have reportedly been found effective for tumor control and for promoting a better quality of life in patients. In this article the authors analyzed the outcomes in 17 patients with skull base chordomas who were surgically treated at Kobe University Hospital between 1972 and 2000. Preoperative radiological examinations included magnetic resonance imaging, computerized tomography, angiography, and balloon occlusion test of the internal carotid artery. Among the various surgical approaches used to remove the tumor were the frontoorbitozygomatic, transmaxillary, transcondylar, transsphenoidal, and the transbasal. Total removal was achieved in two (12%), near-total removal in three (18%), subtotal removal in nine (52%), and partial removal in three patients (18%). Since 1990, chordomas have been radically resected via various skull base approaches; the combined total or near-total removal rate has been 80% in this period. Radical removal of the tumors has not led to an increased risk. At the final follow-up review (mean 59.5 month), 75% of the patients were still alive, and 25% had died of chordoma recurrence. The overall recurrence-free survival rate was 82% at 3 years and 51% at 5 years. The 5-year recurrence-free survival rate in the five patients who underwent the operation during the past decade was 77% (mean follow up of 5.2 years). In two patients with recurrent tumors who underwent radiosurgery, no evidence of tumor regrowth was demonstrated at 3 years posttreatment. The authors suggest that for the treatment of skull base chordomas radical resection is a key factor for longer survival and improved quality of life. Patients with sufficiently small tumors, which show a favorable configuration and location, can be suitable candidates for stereotactic radiosurgery.

Clinicopathologic and cytogenetic analysis of malignant rhabdoid tumor of the central nervous system

Malignant rhabdoid tumor (MRT) is an aggressive Case 1 neoplasm of infants and children with distinctive light microscopic, immunohistochemical, and ultrastructural features [1, 2]. Originally described in the kidney, the tumor also occurs in the liver [3], soft tissues [4], and paravertebral region [5]. Primary neoplasms of the brain such as primitive neuroectodermal tumors and astrocytomas have been found to arise in some patients with systemic MRTs [6-9]. Recently, primary MRT of the central nervous system (CNS MRT), unassociated with systemic tumors, has been described [1, 2,10-19]. In the sixteen reported cases for which clinical information is available, these tumors appear to be similar to nonCNS MRTs in that they are aggressive, and usually fatal. Abnormalities of chromosome 22 have been reported in four of five CNS MRTs in which cytogenetic analysis has been done [14, 20-22]; four of fourteen of the histologically similar non-CNS Case2 MRTs have abnormalities of chromosome 22 [3, 5, 22-26]. Because this primary brain tumor has been recognized less than a decade, and the number of karyotyped cases is small, we report three additional cases diagnosed at our pediatric hospital in the last three years. The combined clinical, histological, immunohistochemical, ultrastructural and cytogenetic studies in these three cases add to the evolving body of information about this unusual childhood CNS tumor. A previously healthy 3-year-old boy presented with lethargy, vomiting, and weakness of the right arm of one week's duration. On neurological examination, he had mild hemiparesis and right-sided hyperreflexia. Magnetic resonance imaging (MRI) showed a 6 cm inhomogeneous mass, with surrounding edema, in the left frontoparietal area. No other masses were seen on body computerized tomography (CT). The patient underwent a left frontal craniotomy with subtotal tumor resection. Postoperatively, he received 5,400 cGy of cranial irradiation. Follow-up head CR showed no evidence of tumor regrowth or craniospinal metastasis. He remains with mild residual right-sided weakness 3 years after surgery.

Brachytherapy of recurrent malignant brain tumors with removable high-activity iodine-125 sources.

Thirty-seven patients harboring recurrent malignant primary or metastatic brain tumors were treated by 40 implantations of high-activity iodine-125 (125I) sources. All patients had been treated with irradiation and most had been treated with chemotherapeutic agents, primarily nitrosoureas. Implantations were performed using computerized tomography (CT)-directed stereotaxy; 125I sources were held in one or more afterloaded catheters that were removed after the desired dose (minimum tumor dose of 3000 to 12,000 rads) had been delivered. Patients were followed with sequential neurological examinations and CT scans. Results of 34 implantation procedures were evaluable: 18 produced documented tumor regression (response) for 4 to 13+ months; five, performed in deteriorating patients, resulted in disease stability for 4 to 12 months. The overall response rate was 68%. In 11 patients, implantation did not halt clinical deterioration. At exploratory craniotomy 5 to 12 months after implantation, focal radiation necrosis was documented in two patients whose tumor had responded initially and then progressed, and in three patients whose disease had progressed initially (four glioblastomas, one anaplastic astrocytoma); histologically identifiable tumor was documented in two of these patients. All improved after resection of the focal necrotic mass and are still alive 10, 15, 19, 24, and 25 months after the initial implantation procedure; only one patient has evidence of tumor regrowth. The median follow-up period after implantation for the malignant glioma (anaplastic astrocytoma and glioblastoma multiforme) group is 9 months, with 48% of patients still surviving. While direct comparison with the results of chemotherapy is difficult, results obtained in this patient group with interstitial brachytherapy are probably superior to results obtained with chemotherapy.

Ameloblastoma and keratinizing ameloblastoma in dogs.

Ameloblastomas reviewed in this report were locally invasive neoplasms arising from the epithelial structures of the dental lamina, and were characterized histologically by features which are unique to dental lamina epithelium. These include the formation of epithelial sheets in which the cells nearest the stroma form a palisading row aligned perpendicularly to the basement membrane and the cells toward the center separate from each other except at desmosomal attachments. This is similar to the appearance of th stellate reticulum of the early enamel organ. Other features include epithelial cords which branch and interconnect, and the intimate association of epithelial structures and collagenous matrix. In our dogs, other important features were the deposition of inclusions similar in appearance to enamel matrix between the cells of the epithelium and various degrees of keratinization. All ameloblastomas studied were locally invasive tumors which occurred at various sites on the gingiva. The average age of the dogs was 8.7 years and the age range was three to 13 years. Radiographically, all of the tumors studied resulted in periodontal osteolysis. Six dogs were treated with radiation therapy, but details of the radiotherapy of two dogs could not be located. Of the other four dogs, one is alive 48 months after radiotherapy with no evidence of tumor regrowth. Regrowth of the oral tumor was apparent in the other three dogs six, 21, and 34 months after completion of the radiotherapy. Three dogs were treated by radical mandibulectomy; all are alive with no evidence of tumor recurrence at two, 20, and 28 months postoperatively. Two dogs had local dissection (curettage) of tumors and the tumors recurred at 12 and 15 months after surgery. One dog was euthanatized after diagnosis of the oral tumor because of a progressive neuropathy.

The Use of C150 and 1502 Steady-State Imaging to Monitor Radiation Treatment Effects

Methods for monitoring the response of tumor and normal tissues to radiation therapy are extremely limited. Development of a method for monitoring physiologic parameters of these tissues sensitive enough to provide evidence of tumor regrowth and possibly predicting unacceptable effects upon normal tissues at an early time would be highly desirable. The aim of this preliminary study was to determine if serial C150 and 1502 steady-state images taken before, during and post-radiation therapy would show changes sufficiently large to suggest their application as therapy monitoring methods. A canine with a spontaneous osteosarcoma in the distal tibia was treated with a two week course of cobalt-60 radiotherapy and monitored. The ratio of tumor to contralateral control first increased in both the C150 and 1502 images to 170 and 140%, respectively, and then gradually decreased to 80 and 60% of their initial values by day 39. When venous blood normalized C150 images were subtracted from 1502 images taken on the same day, the decrease at day 39 reached 60%. The large changes observed in this study provides positive evidence that these methods may prove useful as monitors for radiotherapy treatment.

Streptozocin-Treated Verner-Morrison Syndrome

A patient with watery diarrhea, hypokalemia, hypochlorhydria, and a non-beta islet cell carcinoma of the pancreas (Verner-Morrison syndrome) was found to have an elevated vasoactive intestinal peptide (VIP) concentration in the plasma as well as in the tumor. Treatment with streptozocin resulted in a dramatic subjective and objective tumor response in this patient. Plasma VIP concentration fell into the normal range after four courses of treatment, diarrhea ceased after the third course of therapy, and measurable tumor mass markedly decreased during that same period of time. The patient remains in clinical remission with no evidence of tumor regrowth 18 months after the beginning of treatment. In this patient, plasma VIP measurements were an excellent marker of tumor activity and correlated well with objective disease measurements and clinical response.