Strontium-89 (Metastron) and the bisphosphonate olpadronate reduce the incidence of spinal cord compression in patients with hormone-refractory prostate cancer metastatic to the skeleton

Spinal cord compression (SCC) is a devastating complication of metastatic cancer. We investigated the potential beneficial effect of two palliative therapies--strontium-89 (Metastron) and the nitrogen-containing bisphosphonate olpadronate--on the incidence of SCC in hormone-refractory prostate cancer (HRPC) metastatic to the skeleton. We retrospectively studied 415 patients with histologically proven prostate cancer who underwent bone scintigraphy at the time of diagnosis and were followed up at the Leiden University Medical Center between 1990 and 1999. Medical or surgical castration was undertaken in 172 patients with evidence for skeletal metastases. Within 2 years, 147 of these patients (85%) developed HRPC associated with severe progressive bone pain. Palliative treatment was given to 131 patients in the form of local radiotherapy ( n=10), 89Sr ( n=46) or intravenous olpadronate ( n=66), with ( n=57) or without ( n=9) maintenance oral olpadronate. Nine patients received both 89Sr and olpadronate at various intervals. Sixteen patients who did not receive any of these treatments were used as historical controls. There was no significant difference in baseline characteristics between treatment modalities. The incidence of SCC was 17% in the whole group, and highest in controls receiving no palliation (50%). None of the patients treated with local radiotherapy, only 4% of patients receiving 89Sr and 21% of patients given olpadronate developed this complication. Our findings suggest a significant reduction in SCC in patients with symptomatic HRPC metastatic to the skeleton who receive palliative therapies. Local radiotherapy completely prevents the incidence of SCC, 89Sr leads to an important decrease in this complication and olpadronate induces a significant, albeit smaller decrease in the incidence of SCC. The use of these agents opens new avenues in the difficult management of patients with advanced prostate cancer who are most at risk of developing SCC.     

Treatment of Primary Tracheal Carcinoma

BACKGROUND AND PURPOSE: In a retrospective study the role of radiation therapy for the treatment of primary tracheal carcinoma was investigated. PATIENTS AND METHODS: Between 1984 and 1997, 25 patients with primary tracheal carcinoma were treated with external beam radiotherapy (17 squamous-cell carcinoma [SCC], 8 adenoid cystic carcinoma [ACC], median dose SCC 60 Gy. ACC 55 Gy). An additional brachytherapy boost was carried out in 10/25 patients (median dose SCC 18 Gy, ACC 15 Gy). Ten patients underwent operative treatment. RESULTS: The median survival (Kaplan-Meier) for patients with SCC was 33 months (ACC 94.2). The 1-, 2- and 5-year survival rates (Kaplan-Meier) for patients with SCC were 64.7% (ACC 85.7%), 64.7% (ACC 85.7%), and 26% (ACC 85.7%). Patients with ACC and patients with a complete remission after treatment had a significantly better survival probability (log rank test, p < 0.05). An excellent or good relief of clinical symptoms was achieved in 88% of the patients with SCC (ACC 88%). Eleven patients were locally controlled at last follow-up (SCC: 5/17; ACC: 6/8). Grade 1 to 2 toxicity (RTOG/EORTC) occurred in 12% (SCC: 2/17, ACC: 1/8) and Grade 3 to 4 toxicity in 8% (SCC: 0/17, ACC: 2/8) of the patients. Persistent or progressive local disease caused complications in 5 patients (fatal hemorrhage n = 2, esophagotracheal fistula n = 2, tracheal necrosis n = 1). CONCLUSION: Radiation therapy is an effective treatment for primary tracheal neoplasms. Surgery followed by adjuvant radiotherapy and primary radiotherapy in inoperable cases represent potentially curative treatment options. Prospective multicenter studies are needed to determine the optimal radiotherapeutic approach.     

Early-onset symptomatic radiation necrosis after stereotactic radiosurgery in the setting of COVID-19 infection

In this brief report, we describe the case of a previously healthy 51-year gentleman who was treated with stereotactic radiosurgery to a dose of 12 Gy to a small right-sided vestibular schwannoma. MRI of the brain performed after treatment revealed stable treated disease but subsequently, the patient developed symptomatic COVID-19 based on PCR along with multiple cranial neurologic deficits, including right facial paralysis, hemifacial anesthesia, and anesthesia of the ipsilateral hard palate and tongue. MRI of the brain was repeated and demonstrated radiation necrosis in the adjacent brainstem for which he was treated with Pentoxifylline and Vitamin E, dexamethasone, and Bevacizumab with only partial improvement. The dose-volume metrics of the brainstem from his radiotherapy plan as well as the trajectory of his imaging findings do not match this clinical picture from radiotherapy alone. We review the basic pathogenesis of the inflammatory response to infection from the SARS-CoV-2 virus as well as the pathogenesis of radiation necrosis. Heightened awareness about potential risks with high-dose radiotherapy in patients with symptomatic COVID-19 should be considered.     

99Tcm(v)-DMSA planar scintigraphy: does it have a role in the management of patients with head and neck squamous carcinoma?

99Tcm(v)-DMSA is a new tumour-imaging agent which has recently been proposed as a scintigraphic marker for head and neck squamous cell carcinoma (SCC). Seventy-seven patients were studied prospectively, of whom 58 had a history and diagnosis of head and neck SCC. All patients were examined, imaged using 99Tcm(v)-DMSA planar scintigraphy and then followed up clinically. In addition, 35 patients were followed up with scintigraphy (81 studies). Scintigraphy was less sensitive and less accurate than clinical examination for the overall detection of patients with SCC, for the detection of patients with SCC at presentation and for the detection of patients with primary tumours, possible nodal disease and with residual and recurrent disease following surgery and irradiation. Approximately 50% of patients exhibited positive uptake of 99Tcm(v)-DMSA in the salivary glands following radiotherapy. Although 99Tcm(v)-DMSA is accumulated at sites of head and neck SCC, its inability to detect low volume disease and apparent low specificity following surgery and irradiation means it has no role to play in the routine evaluation of patients with head and neck SCC.     

The monitoring of gynecological radiotherapy using serial tumor marker determinations

In 149 collum and 45 corpus carcinomas tumor marker concentrations in serum have been measured before, during and sex to eight weeks after termination of radiotherapy. For the collum carcinomas (average of FIGO I to IV) the sensitivity of CEA was found to be 51%, SCC 67%, CEA +SCC 80%. In corpus carcinomas CEA had low sensitivity and could not readily be used for therapy monitoring. However, in a number of cases CA125 was a good substitute. Six to eight weeks after termination of radiotherapy the average tumor marker levels have been declined by comparison with the pretherapeutic values (100%): For the collum carcinoma CEA dropped to 39%, SCC to 57%; for the corpus carcinoma CEA to 72%, CA 125 to 81%. The highest diagnostic information was gained by comparison of post-therapeutical tumor-marker levels with cut off values obtained from healthy women of the same age group. After treatment in 29 of 106 collum carcinomas CEA and or SCC levels did still exceed these cut off values. In eleven cases this marker elevation was due to paraaortic lymph node metastases, in seven cases a local tumor residue was discovered and in six cases general metastases. In corpus carcinomas the main reason for post-therapeutic elevated CA125 values also were paraaortic lymph node metastases. Thus, the use of serial tumor marker determination for control of gynecological radiotherapy is a helpful tool in early detecting local tumor residues and metastases. The decision making for further radiotherapeutical measures will be much easier, if accompanying tumor marker determinations have been done during primary radiotherapy.     

Technetium-99m (v) dimercaptosuccinic acid uptake in patients with head and neck squamous carcinoma: experience in imaging

A recently developed imaging agent, technetium-99m (v) dimercaptosuccinic acid (99mTc (v) DMSA), has been used to assess head and neck squamous carcinoma (SCC). We have prospectively studied 62 patients of whom 53 had a histologically proven head and neck SCC. The remaining nine had benign lesions. The results of planar imaging in patients with primary disease yielded an 85% sensitivity and 78% specificity. Planar imaging in patients with cervical lymphadenopathy revealed a 59% sensitivity. Nineteen patients also had single photon emission computed tomography imaging which improved the image quality, spatial resolution and sensitivity of the investigation. Twenty-seven patients were scanned before and after radiotherapy and, of these, 96% showed positive uptake in the salivary glands with no evidence of tumor recurrence. This study has shown 99mTc (v) DMSA imaging provides a cheap and rapid method of investigating head and neck SCC and further studies are necessary to evaluate its role in the management of patients with this disease.     

Correlation between angiogenesis and reduction ratio measured using<Superscript>201</Superscript>Tl chloride single photon emission computed tomography in patients with oral cavity squamous cell carcinoma

OBJECTIVE: The aim of this study is to examine the correlation between tumor angiogenesis and response to preoperative radiotherapy evaluated using 201Tl single photon emission computed tomography (Tl SPECT) in oral cavity squamous cell carcinoma (SCC). METHODS: Tl SPECTs before and after preoperative radiotherapy were obtained from 11 patients diagnosed with SCC in oral cavity. Regions of interest were set around the tumor and scalp respectively, and the ratio of mean counts in the tumor to those in the scalp was calculated (T/N). Immunohistochemical staining for investigating microvessel density of pre-treatment biopsy specimen was performed using CD31 monoclonal antibody. We compared microvessel density with semi-quantitative parameters obtained using Tl SPECT (T/N at pre- an post-treatment, reduction ratio) and prognosis. RESULTS: The subgroup with higher microvessel density showed a significantly higher reduction ratio than the one with lower microvessel density. Regarding prognosis, the subgroup with locoregional recurrent disease exhibited a significantly higher microvessel density than the one without recurrence. CONCLUSIONS: In SCC of the oral cavity, there was a significant correlation between microvessel density and response to preoperative radiotherapy. Namely, it was revealed that change of 201Tl uptake after preoperative radiotherapy correlated with tumor angiogenesis of oral cavity SCC.     

Case study thoracic radiotherapy in an elderly patient with pacemaker: The issue of pacing leads

To assess clinical outcome of patients with pacemaker treated with thoracic radiation therapy for T8-T9 paravertebral chloroma. A 92-year-old male patient with chloroma presenting as paravertebral painful and compressive (T8-T9) mass was referred for radiotherapy in the Department of Radiation Oncology, Institut Curie. The patient presented with cardiac dysfunction and a permanent pacemaker that had been implanted prior. The decision of Multidisciplinary Meeting was to deliver 30 Gy in 10 fractions for reducing the symptoms and controlling the tumor growth. The patient received a total dose of 30 Gy in 10 fractions using 4-field conformal radiotherapy with 20-MV photons. The dose to pacemaker was 0.1 Gy but a part of the pacing leads was in the irradiation fields. The patient was treated the first time in the presence of his radiation oncologist and an intensive care unit doctor. Moreover, the function of his pacemaker was monitored during the entire radiotherapy course. No change in pacemaker function was observed during any of the radiotherapy fractions. The radiotherapy was very well tolerated without any side effects. The function of the pacemaker was checked before and after the radiotherapy treatment by the cardiologist and no pacemaker dysfunction was observed. Although updated guidelines are needed with acceptable dose criteria for implantable cardiac devices, it is possible to treat patients with these devices and parts encroaching on the radiation field. This case report shows we were able to safely treat our patient through a multidisciplinary approach, monitoring the patient during each step of the treatment.     

Arthritis associated with HIV infection: radiographic manifestations

Radiographs of symptomatic joints were retrospectively evaluated in 24 patients with inflammatory arthritis and human immunodeficiency virus (HIV) infection. Clinically, 20 patients had a seronegative arthritis including Reiter syndrome (54%), psoriatic arthritis (17%), and undifferentiated forms of spondyloarthropathy (13%). These patients were indistinguishable radiographically from patients with typical seronegative disorders except for the predominance of lower-extremity abnormalities. Four patients (17%) had a rheumatoidlike arthritis defined as acute symmetric polyarthritis (ASP). With the exception of extensive proliferative periostitis, ASP simulated classic rheumatoid arthritis. HIV-associated arthritis was manifest during various stages of HIV infection. It preceded acquired immunodeficiency syndrome in 64% of patients with stage IV HIV infection. Awareness of the coexistence of HIV infection in patients with the above-mentioned arthritides is important, since immunosuppressive therapy, commonly used in the treatment of arthritis, can have detrimental effects in patients with HIV infection.     

The combination of ionizing radiation and expression of a wild type p53 gene via recombinant adenovirus induced a prominent tumour suppressing effect in human oral squamous cell carcinoma

Human oral squamous cell carcinoma (SCC) cell lines HSC4 and SAS were infected with wild type p53 (wt-p53)-encoding adenovirus (AxCAip53) and subsequently irradiated to investigate the effectiveness of p53 gene therapy in combination with radiation therapy for treating oral SCC. Western blot analysis using anti-p53 monoclonal antibody showed that a large amount of mutant p53 protein was accumulated in HSC4 cells, while no detectable p53 protein was observed in SAS cells. The induction of p53 expression by AxCAip53 infection was clearly observed in both HSC4 and SAS cells. A clonogenic cell survival assay demonstrated that AxCAip53 infection alone, or X-irradiation alone, significantly inhibited the growth of cancer cells, but that combined treatment was most effective, even in mutant p53-accumulated HSC4 cells. Flow cytometric analysis showed that the apoptotic pathway was induced in virus treated and radiation treated cells. Taken together, these findings suggest that the combination of p53 gene therapy and radiation therapy has a possibility to effectively treat oral SCC defective in p53 function.     

Intensity-modulated radiotherapy: examples of its utility in head and neck cancer

Intensity-modulated radiotherapy (IMRT) has been available at Peter MaCallum Cancer Centre (PMCC) since November 2000. The present report illustrates two cases of our early experience with IMRT. Case 1 is a 66-year-old man with a T(1)N(2)M(0) nasopharyngeal carcinoma treated with chemo-radiotherapy using parotid-sparing IMRT. Fourteen months following treatment he remains in complete remission, with salivary function assessed using a xerostomia-specific quality of life questionnaire, having returned to near pretreatment levels by 12 months. Case 2 is a 70-year-old man with a T(4)N(0)M(0) base of tongue squamous cell carcinoma treated with chemo-radiotherapy after refusing radical surgery. He had received subtotal nodal irradiation to 36 Gy in 1994 for Hodgkins disease stage IIA. A radical dose was still achievable despite previous irradiation without exceeding unacceptable spinal cord dose with IMRT. He remains in complete remission 14 months from his initial presentation without evidence of neurological toxicity. Intensity-modulated radiotherapy allows sparing of critical normal structures in the head and neck without compromising dose to the tumour. It is, therefore, desirable for several clinical applications and essential in some, if unacceptable compromises are not to be made.     

A forensic autopsy case of death from laryngeal stenosis due to a late complication of radiotherapy

Irradiation is one of the standard modalities of treatment for neck cancer; however, it occasionally causes severe late complications. Here, we report an autopsy case of a death from laryngeal stenosis due to a late complication of radiotherapy. A man in his 70s who underwent radiotherapy for laryngeal cancer 6 months before death was found dead in his home. Complete regression of the cancer was obtained after treatment, and signs suggestive of cancer recurrence were not evident before his death. Postmortem computed tomography showed severe narrowing of the upper airway due to glottic tissue swelling. The autopsy revealed an edematous epiglottis and supraglottic-glottic tissue with an ulcerative lesion, which severely narrowed the upper airway. Histopathological findings showed edema, hyalinization, and a proliferation of granulation tissue at the affected site. Neither a gross recurrence of cancer or finding suggestive of infection was observed in the specimen. This case is instructive to forensic pathologists regarding noting a radiotherapy complication as one of the possible causes of sudden death when the decedent previously underwent radiotherapy for neck cancer, and stresses the importance of detailed history taking and careful examination of the neck organs.     

Autopsy findings of a patient with rapidly progressive massive ascites caused by alcoholic cirrhosis

A 54-year-old man, who lived alone, was hospitalized due to rapid deterioration of the general condition over a three-week period caused by alcoholic cirrhosis. One month after he left hospital, he was found dead in his house by his friend. Three days before he was found dead, he had met his friend and seemed to be in poor condition. Autopsy was conducted by a medical examiner to clarify the cause of death. Externally, signs of severe jaundice were apparent over the whole body, along with extensive abdominal swelling and edema of the extremities. Autopsy findings demonstrated that the abdominal cavity contained an amount of massive turbid and slight pale reddish brown ascites (23 l). There were no findings of severe peritoneal inflammation. The liver (650 g) was elastic hard and had a micro-nodular surface, which showed severe atrophy. Microscopic examination of the liver showed clear pseudolobule with severe fibrosis in the stroma. There were no significant changes in the heart or brain. The stomach was empty and only a slight amount of intestinal contents. There was no ethanol detected in the blood or urine. The direct cause of his death was circulatory dysfunction due to massive accumulation of the ascites. The reasons for the massive ascites accumulation over 20 l in this case were (1) that he had no serious complications other than ascites; and (2) he did not have any medical treatment just before his death.     

Tongue cancer in younger patients

Tongue cancer involving the anterior tongue often presents at an early stage. The aetiology is strongly associated with smoking and alcohol abuse similar to other squamous cell carcinomas (SCC) of the head and neck (HN). Surgery and radiotherapy, either alone or together, offer the prospect of cure in the majority of patients. However, there remains a group of younger patients less than 40 years old for whom outcome is often poor. Presented here is the case of a 24-year-old woman who developed SCC of the anterior tongue. Despite treatment, loco-regional relapse occurred resulting in death. The literature identifies a distinct subgroup of younger patients who develop HN SCC, particularly of the oral cavity. The aetiology remains unclear. Recent studies have looked at the prognostic significance of various new non-clinico-pathological markers in HN SCC (including p53 tumour suppressor gene, cyclin D1 protein, Ki 67 antigen and tumour angiogenesis). The majority of these studies, as expected, have involved the typical HN patient (male, aged > 60 years old). However, the relevance of these studies is of likely importance to all patients diagnosed with HN SCC. The recent use of these non-clinical-pathological markers in HN SCC, including reference to such studies in younger patients, is discussed. The English literature during the past 30 years is reviewed with reference to the diagnosis of tongue SCC in younger patients.     

The impact of missed fractions in head and neck radiotherapy and how they can be minimised

Radiotherapy is an effective treatment for cancer, especially in cases of early stage disease, hence its continued routine use in Oncology. Overall treatment time is a significant factor which influences the efficacy of radiotherapy treatment. The accelerated reproduction of tumour clonogenic cells is considered to be a major contributory cause for reduced local control when treatment time is extended without dose compensation.It has been reported that even a one day gap can be damaging to treatment outcome with a reduction in local control being estimated at 1.4% per day of missed radiotherapy. With recent treatment compliance rates of 48.9% being observed in head and neck radiotherapy patients these factors provide the rationale for such a review. This paper reviews the current literature on the impact of missed fractions in radiotherapy for SCC head and neck and provide recommendations as to how missed fractions can be minimised.     

Prognostic factors for local control and survival in patients with spinal cord compression from myeloma

Background

This retrospective study aimed to identify prognostic factors for local control and survival in 214?patients irradiated for spinal cord compression (SCC) from myeloma.

Patients and methods

Ten potential prognostic factors were investigated including age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), number of involved vertebrae, ambulatory status, other osseous lesions, extraosseous lesions, interval from first diagnosis of myeloma to SCC, time developing motor deficits before radiotherapy (RT), and the RT schedule (short-course vs. long-course RT).

Results

On univariate analysis, no factor was associated with local control of SCC. Survival was associated with ECOG-PS (p?Conclusion New independent prognostic factors were identified for survival after RT of SCC from myeloma. These factors can help tailor treatment to the individual patient.     

Genetic counselling following paternal therapeutic irradiation

We discuss a patient who received adjuvant radiotherapy for stage I seminoma. He was advised to avoid conception for 6 months following treatment. However, his partner became pregnant only shortly after he completed his radiotherapy (i.e. with sperm that had been irradiated). We estimated the dose received by the remaining testis as 30 cGy. Here, we review the information available to advise patients on the risks to the fetus from paternal preconception irradiation. For the population, a doubling dose for hereditary effects of 1 Gy has recently been reaffirmed (United Nations Scientific Committee on the Effects of Atomic Radiation 2001). However, a range of animal studies suggest conception with postmeiotic sperm carries a greater risk of genetic damage than conception with sperm derived from irradiated stem cells. We have attempted to quantify the risks in this particular case. Lead shielding of the testes may reduce radiation received from the primary beam, but internal scatter still produces a risk. In male patients who are potentially fertile, the best advice remains to delay conception after radiotherapy for as long as 6 months. Our case illustrates the need to reinforce such advice.     

Fanconi’s Anemia and Clinical Radiosensitivity

BACKGROUND: Patients with Fanconi's anemia (FA) may exhibit an increased clinical radiosensitivity of various degree, although detailed clinical data are scarce. We report on two cases to underline the possible challenges in the radiotherapy of FA patients. CASE REPORT AND RESULTS: Two 24- and 32-year-old male patients with FA were treated by definitive radiotherapy for locally advanced squamous cell head and neck cancers. In the first patient, long-term tumor control could be achieved after delivery of 67 Gy with a-in part-hyperfractionated split-course treatment regimen and, concurrently, one course of carboplatin followed by salvage neck dissection. Acute toxicity was marked, but no severe treatment-related late effects occurred. 5 years later, additional radiotherapy was administered due to a second (squamous cell carcinoma of the anus) and third (squamous cell carcinoma of the head and neck) primary, which the patient succumbed to. By contrast, the second patient experienced fatal acute hematologic toxicity after delivery of only 8 Gy of hyperfractionated radiotherapy. While the diagnosis FA could be based on flow cytometric analysis of a lymphocyte culture in the second patient, the diagnosis in the first patient had to be confirmed by hypersensitivity to mitomycin of a fibroblast cell line due to complete somatic lymphohematopoietic mosaicism. In this patient, phenotype complementation and molecular genetic analysis revealed a pathogenic mutation in the FANCA gene. The first patient has not been considered to have FA until he presented with his second tumor. CONCLUSION: FA has to be considered in patients presenting at young age with squamous cell carcinoma of the head and neck or anus. The diagnosis FA is of immediate importance for guiding the optimal choice of treatment. Radiotherapy or even radiochemotherapy seems to be feasible and effective in individual cases.     

Radiation treatment of superficial spreading carcinoma of the esophagus

Superficial spreading carcinoma of the esophagus is a relatively rare disease. A 78-year-old man with this lesion was treated with high-dose-rate intracavitary irradiation (6 Gy) following external irradiation (48 Gy). The irradiated length was very long: 21 cm for intracavitary irradiation, which covered almost the entire thoracic esophagus, and 24 cm for external irradiation, which covered the entire thoracic esophagus. After treatment, he was well and could eat solid foods until his death, without tumor, two years and five months after radiotherapy. Intracavitary irradiation with a long irradiation length following external irradiation with a long irradiation length is recommended for the treatment of superficial spreading carcinoma of the esophagus.