Indrajit Fernando

The effect of head and neck irradiation on taste dysfunction: a prospective study.

Taste loss is a major cause of morbidity in patients undergoing head and neck irradiation. In a prospective study, 26 patients undergoing radical head and neck irradiation at the Royal Marsden Hospital, Sutton, and the Queen Elizabeth Hospital, Birmingham, were assessed for taste loss and xerostomia. Taste was tested using a subjective questionnaire and by objective taste testing with a series of solute solutions (sucrose, sodium chloride, urea and hydrochloric acid) at increasing concentrations, to determine the threshold level of taste sensation, both before and after radiotherapy. Xerostomia was assessed using a patient questionnaire. The volume of tongue and parotid contained within the high dose volume of the radiation treatment field was determined for each patient and correlated with the degree of objective and subjective taste loss as well as the degree of xerostomia. The results have shown that both objective (r = 0.59; P = 0.0016) and subjective taste loss (r = 0.78; P = 0.0001) was significantly associated with the proportion of tongue, but not parotid, contained within the radiation treatment field. The data gave no evidence to suggest any relationship between recovery of taste loss and volume of parotid or tongue irradiated. However, recovery of subjective taste loss, 1 month after completing radiotherapy was seen in two patients, both of whom had been treated using a wedge pair technique to avoid the contralateral area of the tongue. Changes in xerostomia were significantly correlated with the proportions of both tongue (r = 0.54; P = 0.004) and parotid (r = 0.82; P = 0.0001) within the radiation treatment fields.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary Squamous Cell Carcinoma of the Breast: Achieving Long-Term Control With Cisplatin-Based Chemotherapy

Pure primary squamous cell carcinoma (SCC) of the breast is rare and difficult to treat. Published series suggest a poor response to conventional breast chemotherapy. A 66-year-old woman with locally advanced SCC of the breast received combined-modality treatment with high-dose radiation therapy (59 Gy in 22 fractions); mastectomy; and chemotherapy with cisplatin 50 mg/m(2), mitomycin-C 6 mg/m(2), and ifosfamide 3 g/m(2) given in 21-day cycles. She remained disease free for 10 years from presentation and died from an unrelated cause. We would suggest that this case lends support to the use of high-dose radiation therapy and platinum-based chemotherapy in the management of this difficult condition.

Fatal Clostridium difficile infection associated with vinorelbine chemotherapy: case report and literature review

Differentiating between chemotherapy-related diarrhoea and Clostridium difficile-associated diarrhoea (CDAD) can be extremely difficult. There is increasing evidence that CDAD can be seen in patients on chemotherapy without prior antibiotic usage. We report the first case of CDAD secondary to vinorelbine chemotherapy and review the literature.

Is there a role for adjuvant hysterectomy after suboptimal concurrent chemoradiation in cervical carcinoma

AIMSnFailure to carry out intracavitary brachytherapy (ICBT) in cervical carcinoma results in suboptimal chemoradiation and increases the risk of recurrence. The aim of this study was to investigate the role of adjuvant hysterectomy after unsuccessful ICBT.nnnMATERIALS AND METHODSnA retrospective analysis was carried out of all women referred with cervical carcinoma between January 1999 and July 2007 where ICBT insertion was unsuccessful after the initial chemoradiation. The data collected and analysed included histology, stage of disease, causes for unsuccessful ICBT insertion, the response to the initial chemoradiation, subsequent treatment, morbidity, recurrence rates and survival rates. Kaplan-Meier and Log-rank methods were used to analyse recurrence-free and overall survival rates.nnnRESULTSnICBT insertion was unsuccessful in 19 of 208 (9%) patients. The causes of failure were: inability to dilate the cervix; uterine perforation; vesicovaginal fistula; patient refusal; other problems, including the presence of pyometrium, patient not fit for general anaesthetic, and narrow vagina; and consultant choice with no obvious reason. Fourteen of 19 patients (74%) received further pelvic external beam radiotherapy (EBRT) alone; five (26%) patients underwent adjuvant hysterectomy. The median follow-up for all patients was 63 months; 60 months for patients treated with adjuvant hysterectomy (range 31-68 months) and 85 months for patients treated with further EBRT. None of the patients treated with adjuvant hysterectomy developed any significant late toxicity. Seven patients (50%) treated with EBRT have relapsed compared with none in the adjuvant hysterectomy arm (P=0.068). Six patients (43%) in the EBRT arm have subsequently died of recurrent disease compared with none in the adjuvant hysterectomy arm (P=0.152).nnnCONCLUSIONSnAdjuvant hysterectomy after unsuccessful ICBT does not seem to increase late toxicity and reduces the risk of pelvic recurrence and may improve survival. The role of adjuvant hysterectomy after suboptimal chemoradiation merits further investigation in clinical trials.

Prolonged Relapse-Free Survival in Two Patients With an Isolated Brain Metastasis From Epithelial Ovarian Carcinoma

Six weeks after total abdominal hysterectomy, bilateral salpingooophorectomy, infracolic omentectomy, and peritoneal washings, a 51-year-old woman with International Federation of Gynecology and Obstetrics stage B moderately differentiated ovarian cystadenocarcinoma had a persistently elevated CA-125 level of 340 mU/L (baseline, 767 mU/L). There was no evidence of residual disease on a contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis. Therefore, she completed six cycles of adjuvant carboplatin (area under the curve 6) chemotherapy, administered every 3 weeks, in August 1997, with normalization of the CA-125 level. In November 1999, the patient developed symptoms of altered consciousness level, left-sided hemiparesis and ataxia, and an episode of Jacksonian epilepsy. A contrast-enhanced CT scan demonstrated a solitary 2.5-cm, space-occupying lesion (SOL) in the right parietal lobe. CT scan of the chest, abdomen, and pelvis and a bone scan failed to demonstrate metastatic disease elsewhere, and the CA-125 level was normal. After discussion at the gynecology and neurosurgery tumor boards, she proceeded to craniotomy and macroscopic debulking of the tumor. Histology confirmed a completely excised, poorly differentiated adenocarcinoma with a papillary pattern (Fig 1) compatible with metastatic epithelial ovarian carcinoma (mEOC). After surgery, she received whole-brain radiotherapy (WBRT; 30 Gy in 10 fractions with 6-MV parallel opposed fields) followed by a right parietal boost (12.5 Gy in five fractions using a three-field planned volume). Treatment was completed in March 2000. In the absence of metastatic disease elsewhere, further chemotherapy was not given. The patient remains relapse free 9 years later, with no evidence of recurrence on CT or magnetic resonance imaging scan of the brain, which show features consistent with a previous craniotomy and changes from previous irradiation (Fig 2). There is no evidence of systemic recurrence on CT scan of the chest, abdomen, and pelvis. Furthermore, the patient has no neurologic deficit or cognitive dysfunction despite her multimodality treatment. A 50-year-old woman with a 2-month history of abdominal distension and CA-125 level of 3,784 mU/L underwent total abdomen hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, and peritoneal washings in June 1997 for International Federation of Gynecology and Obstetrics stage IIIC mixed epithelial ovarian carcinoma, followed by six cycles of adjuvant carboplatin (600 mg) chemotherapy, administered every 3 weeks, which she completed in November 1997. CT of the chest, abdomen, and pelvis on completion of treatment showed no evidence of mEOC, and the CA-125 level was 4 mU/L. In August 1999, she developed headaches, and a CT scan demonstrated an SOL in the left frontal lobe. CT scan of the chest, abdomen, and pelvis did not show metastatic disease, and the CA-125 level was 12 mU/L. A craniotomy and macroscopic debulking of tumor was performed after discussion at the tumor board, and histology confirmed a moderately differentiated papillary serous carcinoma. After surgery, she proceeded to WBRT (30 Gy in 15 fractions using 6-MV parallel opposed fields) followed by a left frontal boost (15 Gy in 10 fractions with a three-field planned volume). In January 2001, she developed recurrent headaches, and a 2-cm solitary SOL was noted in the left anterior cerebrum on magnetic resonance imaging scan. Her disease progressed within 6 months of treatment with stereotactic radiosurgery and despite three cycles of chemotherapy with carboplatin (area under the curve 5) and paclitaxel (175 mg/m), administered every 3 weeks, commenced in July 2001. Because she had no evidence of metastatic disease elsewhere on further imaging, she underwent a second craniotomy and debulking procedure, and histology confirmed mEOC. She remains alive and relapse free 8 years after the second craniotomy. Isolated brain metastasis (BM) from mEOC is poorly described in the literature. The incidence of BM from mEOC is 1%. This rate may increase as women with mEOC live longer as a result of the availability of multiple lines of chemotherapy and as improved radiologic imaging increases detection of smaller metastatic deposits. The median survival time of women with BM from mEOC ranges from 3 to 12 months despite multimodality treatment including surgery, radiotherapy, and chemotherapy. Multiple BMs and the presence of systemic metastatic disease are poor prognostic factors. Approximately 45% of women with EOCassociated BM have an isolated metastasis. The recommended treatment includes debulking surgery followed by radiotherapy, provided that the functional capacity is not severely compromised. This combined approach is associated with a more favorable outcome compared with treatment with palliative WBRT Fig 1. JOURNAL OF CLINICAL ONCOLOGY D I A G N O S I S I N O N C O L O G Y VOLUME 28 NUMBER 17 JUNE 1

Survival and toxicity following chemoradiation for carcinoma of the cervix: Impact of multiple phase treatment and shielding.

AIMnWe report on outcomes and significant grade 3-4 late toxicities between January 1999 and October 2006 following introduction of multi-phase treatment and effect of shielding in treatment of cervical cancer with concurrent chemoradiation.nnnPATIENTS AND METHODSnRadiotherapy dose by phase, recurrence, survival and toxicity data was collated by a retrospective review of clinical notes. Shielding information was retrieved from original planning films.nnnRESULTSn3-year survival for stages I, II and III disease were 89%,76% and 51% respectively. Local pelvic failure was 9%. Overall significant late toxicity (SLT) rate was 13%, with lower rates for post-operative treatment than primary chemoradiation (4% vs. 16%). SLT with single phase treatment was 29% versus 12% following multiphase EBRT and 16% when <2 areas were shielded versus 6% with ≥3 shielded areas (p=0.01).nnnCONCLUSIONnShielding and multi-phase treatment not only reduce dose to organs at-risk but can also reduce late toxicity without compromising local control or survival.

Prolonged trastuzumab therapy in a patient with recurrent breast cancer and anthracycline-induced cardiac failure

Current practice precludes patients with pre-existing cardiac dysfunction from trastuzumab therapy. A 57-year-old patient with HER2 positive metastatic breast cancer and anthracycline-induced cardiac failure was safely treated with trastuzumab. At 46 months, left ventricular ejection fraction (LVEF) did fall to 38.3%, but 8 months later has recovered to 47%. She remains disease free and asymptomatic from cardiac dysfunction more than 6 years following breast cancer recurrence. We review the evidence for the use of trastuzumab in patients with controlled cardiac dysfunction, and suggest this group of patients should be considered for treatment with trastuzumab if no other or only less efficacious therapeutic options are available.