Meningeal hematopoiesis following radiation myelitis in a hematopoietic stem-cell transplant recipient

Extramedullary meningeal hematopoiesis (EMH) represents an uncommon finding after stem-cell transplantation. We describe the case of an allogeneic bone marrow transplantation (BMT) recipient who developed EMH 1 month after radiation myelitis had been diagnosed. A 39-year-old man with multiple myeloma underwent matched unrelated BMT following a myeloablative conditioning regimen of cyclophosphamide and total-body irradiation (200 cGyx6). This was followed by delivery of 40 Gy of involved-field radiation to an extramedullary plasmacytoma compressing the spinal cord. Although transplantation went extremely well, the patient developed radiation myelitis 7 months after transplantation, and EMH ensued 1 month later. Because the patient was not in a disease state known to cause EMH, it is tempting to speculate that radiation-related neural injuries might cause donor cells to migrate to the central nervous system.     

Recurrence patterns of mucose-associated lymphoid tissue lymphoma after definitive radiation treatment: A single center experience

Objectives: To evaluate the treatment outcomes in non-gastric and non-nodal mucose-associated lymphoid tissue (MALT) lymphoma patients treated by definitive radiation therapy (RT).

Methods: A total of 134 patients were analyzed. The RT dose was 30.6 or 36?Gy.

Results: The median follow-up duration for all patients was 51.1 months (range, 3.0–132.4 months). Among the 88 orbital MALT lymphoma patients, 12 had disease recurrence. There were 23 head and neck tumor patients. Two patients experienced relapse, all at out-of-field locations. Gastrointestinal MALT lymphoma was diagnosed in 13 patients, and three showed local (n?=?1), distant (n?=?1), or local/distant (n?=?1) relapse.

Conclusion: RT alone is highly effective in achieving local control and long-term survival in localized MALT lymphoma. In orbital MALT, excellent local control is achieved, and relapse is predominantly observed in the contralateral eye. Other head and neck lymphomas are also well controlled.     

Atopy and neural damage

The occurrence of myelitis with atopic diathesis (atopic myelitis) affecting young adults has recently been noted in Japan. The disease preferentially affects the posterior column of the cervical spinal cord, as shown clinically and by MRI. It is characterized by hyperIgEaemia and the presence of mite antigen-specific IgE. The spinal cord lesions have been shown to be eosinophilic inflammation on biopsy and thus an allergic mechanism is thought to be operative in this condition. In addition, we also found that Hirayama disease, juvenile muscular atrophy of the distal upper extremity, is also associated with airway allergy such as allergic rhinitis and atopic asthma. In children, poliomyelitislike illness after acute asthma attacks is well known as Hopkins syndrome. Moreover, by the prospective study of the history of allergic disorders in common neurologic diseases, an association between spinal progressive muscular atrophy (SPMA) and asthma as well as between myelitis and atopic dermatitis has been demonstrated. These observations strongly suggest a link between atopic diathesis and spinal cord damage. Central nervous system damage associated with atopic diathesis may be classified into two types; eosinophilic myelitis preferentially affecting the cervical spinal cord and lower motor neuron damage, such as Hopkins syndrome, Hirayama disease and SPMA. The former is typically associated with atopic dermatitis while the latter, with airway allergy.     

Primary biliary cirrhosis, Sjogren's syndrome, and transverse myelitis

A 35-yr-old woman with coexistent primary biliary cirrhosis and Sjogren's syndrome developed recurrent transverse myelitis. The histopathologic appearance was that of an angiitis associated with necrotizing myelopathy involving the cervical and thoracic spinal cord.     

Combination chemotherapy and radiation therapy. The medical management of epidural spinal cord compression from testicular cancer

Radiation and surgery are the mainstays of treatment for epidural spinal cord compression. There are reports in the literature, however, in which the use of chemotherapy alone or in combination with radiation and surgery has resulted in improved patient response. We present two patients with spinal cord compression from testicular cancer who developed progressive paraplegias that were successfully reversed with combination chemotherapy, steroids, and radiotherapy. In one case, the patient was unable to receive more than 600 rad (6 Gy) of radiation and his improvement was clearly related to the chemotherapy he received. In treating tumors causing spinal cord compression that are thought to be chemosensitive, one should consider adding chemotherapy to radiation or using chemotherapy alone if the options of surgery or radiation are not available.     

Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer

INTRODUCTION Cervical esophageal cancer occurs rarely and accounts for only 2%-10% of all esophageal carcinomas in the United States[1]. Surgery, an option only for patients with early-stage tumors, generally requires a total laryngopha ryngoesophagectomy…     

Paclitaxel as a radiation sensitizer for locally advanced pancreatic cancer

Paclitaxel and concurrent radiation (paclitaxel/RT) have been evaluated by the Brown University Oncology Group (BrUOG) and the Radiation Therapy Oncology Group (RTOG) in phase I and II studies for patients with locally advanced pancreatic cancer. The dose limiting toxicities were abdominal pain within the radiation field, nausea and anorexia. The phase II Brown University study, utilizing paclitaxel 50 mg/m(2) per week for 6 weeks with 50.4 Gy radiation, demonstrated modest locoregional activity and acceptable toxicity. The median and 1-year survival of paclitaxel/RT in the RTOG phase II study suggests an improvement over previous RTOG studies of fluorouracil (5-FU) and radiation. The addition of gemcitabine to paclitaxel and radiation has also demonstrated promising preliminary activity and a phase II study by the RTOG is being initiated.     

同时推量加速调强放疗治疗头颈部恶性肿瘤的临床研究

应用同时推量加速调强放疗技术（SIB－IMART）治疗15例头颈部恶性肿瘤，肉眼靶区（GTV）的平均剂量为70Gy，临床靶区（CTV）的平均剂量为54Gy，脑干、脊髓及腮腺等正常组织的受量均在允许范围之内。结果 13例38天内完成治疗，2例因副作用而中断放疗；皮肤反应I级12例、Ⅱ级3例；粘膜反应Ⅱ级9例、Ⅲ级4例、Ⅳ级2例，咽部及食管I级10例、Ⅱ级3例、Ⅲ级2例；唾液腺副作用明显较传统放疗技术轻，15例中0级3例、I级10例、Ⅱ级2例；口干0级3例、I级9例、Ⅱ级3例，无重度或完全口干病例。放疗结束后疗效达CR者13例，PR者2例，无一例出现病情进展。认为SIB－IMART治疗头颈部恶性肿瘤安全可行，特别是肋腺可受到较好保护，且不同的靶区可以同时实现不同的剂量水平，缩短了治疗时间。     

Dose escalation of concurrent hypofractionated radiotherapy and continuous infusion 5-FU-chemotherapy in advanced adenocarcinoma of the pancreas

BACKGROUND/AIMS: To investigate the advantages and palliative effectiveness of concurrent hypofractionated radiotherapy (RT) and chemotherapy (5-FU) in patients with locally advanced and metastatic adenocarcinoma of the pancreas. METHODOLOGY: A total of 26 patients were enrolled in this study. Twenty patients had locally advanced (M0) and 6 patients had metastatic (M1) disease. They were treated with hypofractionated radiation therapy (RT) (4x3 Gy per week) and concurrent continuous infusion (300mg/sqm/24h) of 5-fluorouracil. The RT doses were escalated in 6-Gy increments starting from 24 Gy in 8 fractions in 2 weeks to 30 Gy in 10 fractions in 2.5 weeks and finally to 36 Gy in 12 fractions in 3 weeks. RESULTS: Only 1 (4%) patient experienced grade 3 mucositis, while 12 (46%) patients experienced grade 2 nausea and 1 (4%) patient experienced grade 2 weakness. No patient experienced treatment interruption or dose reduction. Late high-grade (>3) toxicity was not observed, but few patients experienced prolonged hematological toxicity, due to administration of chemotherapy after radiochemotherapy. Pain improved in 70% of the patients. The median survival time for all 26 patients is 8 months, 9 months for locally advanced cancer patients and 5 months for metastatic cancer patients. CONCLUSIONS: Dose escalation to 36 Gy in a hypofractionated manner proved to be feasible with low toxicity in patients with locally advanced and metastatic adenocarcinoma of the pancreas and warrants further investigation aiming at optimal tailoring in these two subgroups of patients.     

Escalated radiation dose alone vs. concurrent chemoradiation for locally advanced and unresectable rectal cancers: results from phase II randomized study

Purpose

This trial was undertaken to compare the rates of resectability between patients treated with neoadjuvant concurrent chemoradiation vs. boosted radiotherapy alone.

Materials and methods

Patients with clinically unresectable rectal cancer were randomized to receive external beam radiation therapy (EBRT) to pelvis (45 Gy) with concurrent oral Capecitabine (CRT group; Arm 1) or EBRT to pelvis (45 Gy) alone followed by 20 Gy dose of localized radiotherapy boost to the primary tumor site (RT with boost group, Arm 2). All patients were assessed for resectability after 6 weeks by clinical examination and by CT scan and those deemed resectable underwent surgery.

Results

A total of 90 patients were randomized, 46 to Arm 1 and 44 to Arm 2. Eighty seven patients (44 in Arm 1 and 41 in Arm 2) completed the prescribed treatment protocol. Overall resectability rate was low in both the groups; R0 resection was achieved in 20 (43 %) patients in Arm 1 vs. 15 (34 %) in Arm 2. Adverse factors that significantly affected the resectability rate in both the groups were extension of tumor to pelvic bones and signet ring cell pathology. Complete pathological response was seen in 7 and 11 %, respectively. There was greater morbidity such as wound infection and delayed wound healing in Arm 2 (16 vs. 40 %; p = 0.03).

Conclusion

Escalated radiation dose without chemotherapy does not achieve higher complete (R0) tumor resectability in locally advanced inoperable rectal cancers, compared to concurrent chemoradiation.     

Comparison of cellular radiosensitivity between different localizations of head and neck squamous-cell carcinoma

The prognosis of carcinomas arising from various sites in the head and neck varies even when the stage of the disease is taken into consideration, e.g. laryngeal carcinoma has a more favourable prognosis compared to oral-cavity malignancies. The purpose of this study was to evaluate intrinsic cellular radiosensitivity as one possible explanation for the observed differences in the survival rates of different anatomical groups. The radiation survival curves were determined for well characterized cell lines derived from laryngeal carcinoma (n=14), pharyngeal carcinoma (n=6), carcinoma of the oral cavity (n=14) and the skin of the face (n=3). The intrinsic radiosensitivity was expressed as area under the survival curve (AUC) values, and this cellular parameter was compared with clinical data and survival of the patients. The intrinsic radiosensitivity in the whole group varied between 1.0 Gy and 2.8 Gy with an average of 1.9 Gy. The mean AUC values for the laryngeal cell lines were 2.0 Gy±0.2, for the oral cavity 1.8±0.3 Gy, for the pharynx 1.8±0.2 Gy and for cutaneous carcinoma 2.1±0.1 Gy. There was a slight difference between the groups of glottic and supraglottic cell lines (mean 1.8±0.2 Gy and 2.1±0.3 Gy, respectively), which is consistent with the differences in clinical curability of these cancers. Otherwise, the differences in cellular radiosensitivity of the carcinoma groups studied did not reach statistical significance. These results indicate that the intrinsic radiosensitivity of squamous-cell carcinoma (SCC) of the larynx does not significantly differ from that of SCC of other sites of the head and neck. Variations in the intrinsic radiosensitivity do not as such seem to explain the observed differences in radiocurability of SCC variously localized in the head and neck.     

Radiation myelitis following allogeneic stem cell transplantation and consolidation radiotherapy for non-Hodgkin's lymphoma

Myelitis is a rare but well documented complication of therapeutic radiation exposure to the spinal cord and is characterized by delayed development of paresthesias, sensory changes and, in severe cases, progressive paresis and paralysis. Although accepted radiation tolerance limits for the spinal cord have successfully limited the incidence of this problem (45-50 Gy, in daily 1.8-2 Gy fractions), aggressive systemic therapy may render patients more susceptible to radiation-related neurotoxicity. We describe the case of a 38-year-old man with refractory non-Hodgkin's lymphoma who underwent matched sibling peripheral blood stem cell transplant following a conditioning regimen of cyclophosphamide (60 mg/kg x 2) and total body irradiation (120 cGy x 11). This was followed by delivery of 30.6 Gy involved-field radiation at 1.8 Gy/day to the mediastinum and left supraclavicular fossa for bulky residual tumor. Although maximum cumulative radiation dose to the spinal cord was less than 45 Gy, the patient subsequently developed progressive lower extremity weakness and MRI abnormalities of the spinal cord limited to the radiation field. This represents the second report in the literature of this unexpected complication, prompting a need to re-examine current guidelines for radiotherapy in the context of high-dose systemic treatment.     

Salvage radiation therapy and chemoradiation therapy for postoperative locoregional recurrence of esophageal cancer

The purpose of this retrospective study was to assess the efficacy of salvage radiation therapy (RT) or chemoradiation therapy (CRT) for locoregional recurrence (LR) of esophageal cancer after curative surgery. Forty‐two patients who received salvage RT or CRT for LR of esophageal cancer after curative surgery between November 2000 and May 2012 were reviewed. The intended RT regimen was 60 Gy in 30 fractions combined with concurrent platinum‐based chemotherapy. Median follow‐up periods were 17.9 months for all evaluable patients and 28.2 months for patients still alive (19 patients) at analysis time. The 1‐, 2‐, and 3‐year survival rates were 81.2 ± 6.4%, 51.3 ± 8.6%, and 41.1 ± 8.7%, respectively, with a median survival time of 24.3 ± 4.1 months. Out of 41 evaluable patients, 16 patients (39%) were alive beyond 2 years from salvage therapy. However, univariate analyses for overall survival showed no significant prognostic factor. Grade 3 or higher leukocytopenia was observed in 46% of the patients. Salvage RT or CRT for LR after surgery for esophageal cancer was safe and effective. These therapies may offer long‐term survival to some patients. RT or CRT should be considered for LR.     

Impact of radiation schedule and chemotherapy duration in definitive chemoradiotherapy regimen for esophageal cancer

Impact of radiotherapy (RT) schedule on local response and duration of the 5-fluorouracil/cisplatin (5 FU/CDDP) chemotherapy (CT) on m are still questioning in chemoradiotherapy (CRT) regimen in esophageal carcinoma.AIM: Evaluate two RT schedules and two different CT durations by a retrospective comparison of the CRT regimens used by two centres between 1994 and 2000. METHODS: In centre I (regimen I), patients received 2 CT concomitantly to a continuous RT (50 Gy/25 fractions/5 weeks). In centre II (regimen II), patients received 6 CT, 3 were concomitant to a split course RT (20 Gy/10 fractions x 3 courses) and 3 CT were delivered after CRT. RESULTS: A total of 129 patients were included, 74 in centre I and 55 in centre II respectively. Main patient characteristics were similar between the two groups. Clinical complete response to CRT was significantly more frequent in regimen I (83.8% vs 65.4%; P=0.02). The median overall survival (OS) was 20 months in regimen I and 22 months in regimen II (NS). During follow-up, responder patients to CRT in regimen II experienced significant fewer metastasis (51.6% vs 27.8%; P=0.03) with a trend to an increased 5-year survival (19.4% vs 11.3%) and OS (26.5 vs 21.0 months) (NS). Grade 3-4 toxicities were not different. CONCLUSION: Clinical complete response to CRT was significantly more frequent with a continuous RT whereas additional CT after CRT significantly reduced metastasis occurrence. CRT regimen in esophageal carcinoma may be more effective using a continuous RT schedule and additional CT courses after CRT completion.     

Tetraplegia After Thyroidectomy in a Patient with Cervical Spondylosis: A Case Report and Literature Review

Cervical spondylosis is degeneration of the cervical spine that occurs during the normal course of aging, and may progress into compression of the spinal cord, or cervical spondylotic myelopathy (CSM), which can cause neurologic dysfunction. Cervical spondylosis can be identified in the majority of people older than 50 years. Many people with cervical spondylosis or CSM are asymptomatic. However, patients with CSM are at higher risk of spinal cord injury (SCI) following minor injury.A 60-year-old woman with asymptomatic cervical spondylosis underwent an elective subtotal thyroidectomy for thyroid nodules. After the surgery, she developed tetraplegia. MRI revealed spinal cord compression and injury. Main diagnoses, therapeutics interventions, and outcomes: Acute cervical SCI was diagnosed. After an emergency anterior cervical corpectomy and fusion surgery, she almost completely recovered.Iatrogenic cervical SCI after nonspinal surgeries that requires neck hyperextension is rarely reported, probably due to underdiagnosis and underreport. Among the 14 cases (including ours) published in the literature, most patients had cervical spondylosis and were senior men. Five patients had diabetes. Four patients had long-term hemodialysis. Seven patients had undergone coronary artery bypass surgery that requires prolonged operative time. Only 3 patients had almost complete recovery. Most patients were disabled. Two patients required tracheostomy for long-term ventilator support. Two patients died. These cases reiterate the potential risk of iatrogenic SCI in people with predisposing conditions such as cervical spondylosis, especially considering the rising prevalence and severity of cervical spondylosis caused by the aging of the population and modern sedentary lifestyle. Surgeries requiring prolonged neck hyperextension put patients with cervical spondylosis at risk for SCI. Failure to recognize the potential occurrence of iatrogenic SCI might endanger patients’ lives.     

Clinical outcomes of radiation therapy for early-stage gastric mucosa-associated lymphoid tissue lymphoma

AIM:To evaluate the clinical outcomes of radiation therapy(RT)for early-stage gastric mucosa-associated lymphoid tissue lymphoma(MALToma).METHODS:The records of 64 patients treated between 1998 and 2011 were analyzed retrospectively.For Helicobacter pylori(H.pylori)-positive patients(n=31),chemotherapy or H.pylori eradication therapy was the initial treatment.In patients with failure after H.pylori eradication,RT was performed.For H.pylorinegative patients(n=33),chemotherapy or RT was the first-line treatment.The median RT dose was 36Gy.The target volume included the entire stomach andthe perigastric lymph node area.RESULTS:All of the patients completed RT without interruption and showed complete remission on endoscopic biopsy after treatment.Over a median follow-up period of 39 mo,the 5-year local control rate was 89%.Salvage therapy was successful in all relapsed patients.Secondary malignancies developed in three patients.The 5-year overall survival rate was 94%.No patient presented symptoms of moderate-to-severe treatmentrelated toxicities during or after RT.CONCLUSION:Radiotherapy results in favorable clinical outcomes in patients with early-stage gastric MALToma who experience failure of H.pylori eradication therapy and those who are H.pylori negative.     

Successful treatment for undifferentiated carcinoma of the esophagus: a case with complete response to chemoradiotherapy

Undifferentiated carcinoma of the esophagus (UEC) is an uncommon esophageal malignancy, and patients with UEC have an especially poor prognosis because of extensive metastasis even at an early stage. A standard treatment regimen for UEC has not yet been established. We have experienced a case with UEC (T2N1, stage II) that achieved complete remission by chemoradiotherapy [cisplatin (CDDP) + 5-fluorouracil (5-FU), 50 Gy]. A 67-year-old man with a 4-cm type 1 tumor in the middle thoracic esophagus was diagnosed as UEC (non-small cell type) histologically. Computerized tomographic (CT) scan of the chest showed metastatic lesions at the right recurrent nerve lymph nodes. Although the lesion was diagnosed as T2, N1, and stage II, the patient was judged to be a severe case because surgical control of UEC is almost impossible even at the early stages. Chemoradiotherapy (CRT; CDDP + 5-FU, and radiation) was selected for this case. In the first course of CRT, the patient was given CDDP (20 mg/m²) and 5-FU (700 mg/m²) for 5 days and concurrent external-beam irradiation (30 Gy, 2 Gy/day × 15 days) in the “long-T” field including the cervical and mediastinal lymph nodes. The second course was the same chemotherapy (CDDP 20 mg/m²/day + 5-FU 700 mg/m²/day, 5 days) with externalbeam irradiation (2 Gy/day) for 10 days (5 days/week, 2 weeks). After the first course of CRT, the patient already had achieved complete remission (CR). An upper gastrointestinal endoscopic study showed the tumor had almost disappeared and was covered by normal epithelium. Histological study from the biopsy samples showed there were no viable cancer cells at the lesion. CT scan of the chest showed the metastatic lesions at the right recurrent nerve lymph nodes had reduced. After the second course of CRT had been completed, the patient was discharged from the hospital. The patient is still alive with no cancer relapse at 2.5 years after the treatment. Further studies to clarify the response rate and survival effect of CRT in patients with UEC are expected.     

Growth hormone therapy in children after cranial/craniospinal radiation therapy: sexually dimorphic outcomes

Radiation therapy (RT) to the craniospinal region in childhood affects final height. The use of GH treatment (GHRx) in children after cranial or craniospinal RT results in variable improvement in final height. Nineteen children (12 males and 7 females) with tumors of the head, treated with cranial or craniospinal RT and subsequently with GHRx, were assessed for final height. Two outcome measures of efficacy of GHRx were used: Y1 = final height SD score (SDS) corrected for genetic potential, using midparental sex-adjusted target height (SATH) SDS, and Y2 = change in height SDS from predicted final height SDS pre-GHRx to actual final height SDS post-GHRx. The median age at diagnosis was 5.4 yr, the median RT to the hypothalamic-pituitary axis was 40 Gy, the median spinal RT dose in 13 of 19 of the subjects treated was 36 Gy, and the median years post-RT to GHRx was 4.8 yr. Adjuvant chemotherapy was used in 12 of 19 patients. All but one (optic glioma) had a lesion anatomically distant from the suprasellar region. The effects of age at diagnosis, sex, L-T4 or GnRH agonist use, conventional vs. hyperfractionated RT, spinal RT, dose of spinal or cranial RT, chemotherapy, peak stimulated GH, dose and duration of GHRx, age at GHRx, time interval between RT and GHRx initiation, bone age, and height SDS at the start of GHRx were also assessed. Y1girls best correlated with younger age at diagnosis and im vs. sc GHRx. Y2girls best correlated with delayed bone age and younger age at diagnosis [Y1girls = -9.95 + 0.38 (age in years at diagnosis) + 3.11[GH method (1 = i.m.; 2 = s.c.)]; r2 = 0.898; P = 0.02; Y2girls = -3.54 + 1.8 (bone age - age in years) + 0.334 (age at diagnosis in years); r2= 0.956; P = 0.02]. Both Y1boys and Y2boys were strongly associated with spinal RT and younger age at diagnosis or treatment [Y1boys = -11.22 + 4.65 [spinal RT (1 = yes; 2 = no)] + 0.396 (age in years at diagnosis); r2= 0.64, P = 0.01; Y2boys = -6.32 + 0.23 (age in years at GH start) + 1.75 [spinal RT (1 = yes; 2 = no)]; r2= 0.646; P < 0.01]. This small historical cohort underscores that final stature is significantly reduced when immature bones are exposed to ionizing radiation. Intramuscular vs. sc use of GHRx is likely to be simply a surrogate marker for earlier methods of treatment. Of note, spinal RT did not significantly impact girls' final heights, whereas in boys, spinal RT strongly predicted ultimate short stature and a reduced response to GHRx. This sexually dichotomous response may be due in part to the greater percentage of spinal growth remaining for boys vs. girls throughout childhood.