A 60-year-old man was visited at the Alessandria Hospital Oncology Unit on August 2011 for a routine visit before a chemotherapy administration (FOLFOX scheme and bevacizumab), complaining of left mandible pain (VAS: visual analogue scale, score 6) and an oral mucosal break; the oral examination revealed a lingual-side bone exposure, 1 cm in diameter (no photo available). Four weeks before, he had started treatment with chemotherapy associated with bevacizumab for the second time.\nHis cancer history had begun on February 2010 with the diagnosis of rectal cancer and lung metastases. He underwent treatment with pelvic radiotherapy and simultaneous chemotherapy (oxaliplatin and fluorouracil in a continuous infusion) and then rectal surgery (on July 2010); additional chemotherapy (FOLFIRI) was administered in August 2010. Some pulmonary metastases were surgically removed on November 2010 but residual disease was still present in a chest postoperative CT scan.\nHe received chemotherapy (FOLFIRI scheme) and bevacizumab (5 mg/kg day 1 every 14 days) between December 2010 and March 2011 (eight cycles over four months). Due to pulmonary progression of the disease, he underwent a short treatment with an experimental agent in another cancer center, suspended on July 2011 due to the diagnosis of brain metastases, treated with radiotherapy. He then started new chemotherapy (FOLFOX scheme) with bevacizumab again.\nHis dental history revealed that he had been submitted for left mandible third molar (3.8) extraction at a private dental office on January 2011 (during the first bevacizumab treatment) without notifying the treating oncologist; the patient complained about incomplete and delayed socket closure after extraction.\nOn August 2011, at an oncology unit visit shortly after the start of the second course of bevacizumab therapy (two administrations), a painful mandible bone exposure was noted and the patient was referred to the Alessandria Hospital ONJ multidisciplinary team; antibiotics (amoxicilline plus clavulanic acid 1 g every 8–12 h and metronidazole 500 mg every 12 h) in combination with a chlorhexidine 0.12% oral rinse were prescribed, with immediate pain reduction. Rx ortopantomography showed no signs of osteolysis but just the profile of the residual socket at the extraction site (). A CT scan without contrast showed a mandible bone cortical lesion in the previous tooth extraction site, 7 mm × 4 mm in size (a–c). Spontaneous expulsion of a bone fragment was referred by the patient two weeks later. The patient was not further visited by the ONJ multidisciplinary team due to death shortly after an episode of pulmonary embolism on October 2011.
Patient D is a 58-year-old white female who was diagnosed with a T2, N0, M0 right sided RCC of clear cell histology in 2001. She underwent radical nephrectomy and was followed by her urologist who found a small enlarging left adrenal mass and numerous pulmonary nodules concerning for metastatic disease in 2005. Metastatic disease was confirmed via biopsy of a lung lesion and the patient was started on high-dose IL-2 (600,000 IU/kg). After 8 weeks, she had disease progression on CT scan in both the lung and adrenal gland. She was then treated with sunitinib 50 mg daily for 4 weeks of a 6 week cycle, in the context of a clinical trial. She required a dose reduction because of pancytopenia. Imaging after 30 weeks showed stable pulmonary disease and improvement of the adrenal lesion and retroperitoneal lymphadenopathy. She remained on sunitinib with stable disease until September 2007 when CT scan showed disease progression in aortocaval lymph nodes. Her treatment was then changed to sorafenib 400 mg BID. She achieved 54 weeks of stable disease until July 2008 when her disease progressed on CT scan. The patient was then put on temsirolimus 25 mg IV weekly until October of 2008 when, once again, she had disease progression on CT scan. She was placed on bevacizumab 10 mg/m2 every 2 weeks and completed 48 weeks of treatment. She then progressed on bevacizumab at all sites and began 6th-line treatment with pazopanib 800 mg daily. She continues to be active and well.